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  • Jefferson Adams

    Can Diet and Mucosal Immune Response Drive Persistent Symptoms in Gluten-Free Celiac Patients?

    Jefferson Adams
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    Reviewed and edited by a celiac disease expert.

      The team compared clinical and serological data and mucosal recovery in 22 celiac patients with no symptoms, and 25 with symptoms, all on a long-term gluten-free diet. 


    Image: CC--euthman
    Caption: Image: CC--euthman

    Celiac.com 05/07/2019 - What causes persistent symptoms in celiac patients who are following a gluten-free diet? Many people with celiac disease suffer from persistent symptoms, even with healthy intestinal mucosa, and while following a gluten-free diet.

    A team of researchers recently set out to explore the role of dietary factors, distinct small-bowel mucosal immune cell types, and epithelial integrity in the perpetuation of gastrointestinal symptoms in gluten-free celiac disease patients.



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    The research team included Pilvi Laurikka, MD; Katri Lindfors, PhD; Mikko Oittinen, MSc; Heini Huhtala, MSc; Teea Salmi, MD, PhD; Marja-Leena Lähdeaho, MD; Tuire PhIlus, MD, PhD; Markku Mäki, MD, PhD; Katri Kaukinen, MD, PhD; and Kalle Kurppa, MD, PhD.

    They are variously affiliated with the Celiac Disease Research Center, Faculty of Medicine and Life Sciences; the Faculty of Social Sciences, Departments of Dermatology, and Internal Medicine, Tampere University Hospital, Faculty of Medicine and Life Sciences, University of Tampere; Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital; Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere; and Seinäjoki Central Hospital, Seinäjoki, Finland.

    The team compared clinical and serological data and mucosal recovery in 22 celiac patients with no symptoms, and 25 with symptoms, all on a long-term gluten-free diet. 

    The team used results from duodenal biopsies to assess the density of CD3+ and γδ+ intraepithelial lymphocytes (IELs), CD25+ and FOXP3+ regulatory T cells, CD117+ mast cells, and the expression of tight junction proteins claudin-3 and occludin, heat shock protein 60, interleukin 15, and Toll-like receptor 2 and 4.

    All subjects followed a gluten-free diet, and showed negative celiac auto-antibodies and clear mucosal healing in the gut. 

    On average, patients with no symptoms showed higher fiber consumption (20.2 vs. 15.2 g/d, P=0.028) and CD3+ IEL density (59.3 vs. 45.0 cell/mm, P=0.045) than patients with ongoing symptoms. There were no differences between the groups in other parameters measured.

    From these results, the researchers conclude that low fiber intake may contribute to ongoing symptoms in celiac patients.  Otherwise, the two groups showed no differences in markers of innate immunity, epithelial stress or epithelial integrity. 

    Higher numbers of IELs in patients with no symptoms suggest a more complex connection between symptoms and mucosal inflammation than researchers had believed. 

    More study will help to shed light on the underlying factors that contribute to persistent symptoms in celiac patients who are following a gluten-free diet.

    Read more at the Journal of Clinical Gastroenterology: March 02, 2018 doi: 10.1097/MCG.0000000000001013

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    Guest Anthony Colatrella

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    A similar study was done in 2015 by Wacklin et al, also from Tempere in Finland,  but the researchers looked at the intestinal microbiota of the 2 groups which was apparently not done in the present study----they found there was a difference in the microbiota of the 2 groups with the group with persistent symptoms having a more proinflammotory microbiota dominated by Proteobacteria while the asymptomatic group had a more "normal" microbiota---leading them to speculate that a restoration of the normal microbiota was necessary for the resolution of symptoms 

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  • About Me

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,500 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.


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