Mashhad University of Medical Sciences. Azita Ganji MD, MPH

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1 Mashhad University of Medical Sciences Azita Ganji MD, MPH

2 CD Food sensitivity (NCGS, ) Food intolerance IBS

5 Gluten translocate through the epithelial mucosa via increased tight junction (TJ) permeability. increases in intraepithelial cell, crypt cell hyperplasia,villous atrophy.

6 enhanced intestinal permeability induced by gluten itself, or by microbiota, or by a combination of both?

7 Intestinal Microbiota and Probiotics in Celiac Disease Luiś Fernando de Sousa Moraes, Lukasz Marcin Grzeskowiak, Tatiana Fiche de Sales Teixeira, Maria do Carmo Gouveia Peluzio Department of Nutrition and Health, Federal University of Vic osa, Vic osa, Minas Gerais, Brazil 2014 review

8 Lactobacillus and Bifidobacterium exert protective properties on epithelial cells from damage caused by gliadin and anti-inflammatory effect. Some microbiota was able to improve intestinal epithelial permeability. lowest levels of production of TNF- and IFN

9 Gluten is not the only issue for CD. genetic background and immune function intestinal permeability Microbiota In CD and other gluten-related disorders, i.e., gluten ataxia, dermatitis herpetiformis, wheat allergy, and non celiac gluten sensitivity.

10 other treatments Genetically modified gluten, zonulin inhibitors, therapeutic vaccines, tissue transglutaminase inhibitors, and, recently, probiotics. Abnormalities in the gut microbiome in CD patients have led to the use of probiotics as an alternative. Some probiotics digest or alter gluten polypeptides. Probiotic modify gut barrier function.

12 PROBIOTICS AND CD To date, the only therapy for CD is GFD. Many patients face difficulties in following a glutenfree diet GFD. The compliance to therapy varies widely, from around 40% to 80 %. Probiotics are an interesting adjuvant in the dietetic management of CD.

13 probiotic VSL#3 VSL#3 (a cocktail of eight strains belonging to the species Bifidobacterium breve, B. longum, B. infantis, Lactobacillus plantarum, L. acidophilus, L. casei, L. del- brueckii subsp. bulgaricus, and Streptococcus thermophilus) In decreasing toxic properties of wheat flour during prolonged fermentation. Was highly effective in hydrolyzing gliadin polypeptides.

14 Marked dysbiosis and an abundance of a peculiar CD- Nf strain characterize the duodenal microbiome in active CD patients thus suggesting that the CDassociated microbiota could contribute to the many inflammatory signals in this disorder.

16 Gluten gluten s main antigen, gliadin. immune system responds to gliadin in distinct ways.

19 NCGS It is not autoimmune enteropathy, and no villous atrophy and crypt hyperplasia and no antibodies to TG2 Although the GI symptoms of patients with NCGS can resemble those associated with celiac disease.

20 Definition of NCGS Gluten leading to intestinal and/or extra- intestinal symptoms. IBS-like symptoms, such as abdominal pain, gas, distension, and irregular bowel movements. extra-intestinal symptoms, including headache or frank migraine, foggy mind, chronic fatigue, joint and muscle pain, tingling of the extremities, leg or arm numbness, eczema, anemia, depression.

21 NCGS Diagnosis by exclusion(cd and wheat allergy ) Elimination diet Open challenge ( reintroduction of gluten) can be used to confirm the diagnosis, based on the rapid reappearance of the intestinal or extra- intestinal symptoms.

22 Food sensitivities Immune-mediated reactions to some nutrients; these reactions (intestinal and extra- intestinal) do not always occur in the same way when people ingest that particular nutrient. NCGS is an example of food sensitivity.

23 Other proteins that are unique to gluten-containing cereals can elicit an innate immune response that leads to NCGS. Wheat sensitivity, rather than gluten sensitivity. Other gluten-containing grains such as barley and rye also can trigger the symptoms.

24 Food sensitivity Food intolerance

25 Food intolerance Body lacks a particular enzyme to digest nutrients. Nutrients are too abundant to be digested completely. Particular nutrient cannot be digested properly.

26 Food intolerance symptoms are exclusively GI and mostly secondary to sugar fermentation by the intestinal microbiota, leading to the production of gas, which causes abdominal distention, abdominal pain, and irregular bowel movements. lactose intolerance. Intolerance to FODMAPs

27 Food intolerance Excess fermentable oligo- and disacchararides, monosaccharides and polyols (FODMAPs) FODMAPs, induce the abdominal symptoms such as bloating. Inhibit, intestinal inflammation, inducing beneficial alterations to intestinal microbiota and generation of SCFA.

28 Sources of FODMAP

29 wheat and rye, when consumed in normal quantities, are only minor sources of FODMAPs

30 Pathogenesis wheat, barley, rye, and their derivatives contain other components, including FODMAPs. FODMAPs cause symptom,limited to intestinal, so we can exclude them from NCGS. Patients with NCGS resolve symptoms after they eliminate gluten- containing grains, despite continuing to ingest FODMAPs from other sources.

31 NCGS and IBS: Are They Synonymous? IBS is a syndrome are different entities with common clinical presentations. It is possible to consider some subjects with NCGS to be typical IBS patients : a subgroup of IBS patients may have NCGS.

32 Coeliac disease presenting with symptoms of irritable bowel syndrome Shahbazkhani et al 11% of patients had CD

33 Clinical Gastroenterology and Hepatology 2016 A dietitian-led GFD provided sustained benefit to patients with IBS-D. The symptoms that improved differed in magnitude according to HLA-DQ status

34 IBS In Northern Europe, the prevalence of IBS in the general adult population is 16% 25%. 30% with IBS-like symptoms, had wheat sensitivity or multiple-food hypersensitivity. In a selected series of adults with IBS, the frequency of NCGS, was 28-30%. This is likely to increase when subjects with primarily extraintestinal symptoms are included.

35 low FODMAP diet vs. Lactobacillus rhamnosus GG in irritable bowel syndrome. World J Gastroenterol 2014 compared a low FODMAP diet with a probiotic (Lactobacillus rhamnosus GG) in the treatment of IBS.

36 Conclusion Microbiota can have important role in pathogenesis and treatment of CD. Large group of patients with GI symptom and excess gas and flatulences can be due to NCGS 30 % of IBS patients have food sensitivity IBS-D patients can be treated with GFD (NCGS)

Food Choices and Alternative Techniques in Management of IBS: Fad Versus Evidence

Food Choices and Alternative Techniques in Management of IBS: Fad Versus Evidence Maria Vazquez Roque, MD, MSc Assistant Professor Gastroenterology and Hepatology 2010 MFMER slide-1 Objectives Gluten-free