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  • Jefferson Adams

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

      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. 

    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.

    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 earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, science, and advanced research, and scientific methods. He previously served as 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.

  • Related Articles

    Jefferson Adams
    Celiac.com 02/09/2015 - Do you suffer from persistent celiac symptoms in spite of following a strict gluten-free diet and having normal small bowel mucosa? Many celiac patients do. Moreover, typical explanations, such as accidental gluten-intake or the presence of other gastrointestinal disease, do not account for all of the symptoms in these patients.
    Recent studies have suggested that changes in intestinal microbiota are associated with autoimmune disorders, including celiac disease.
    A team of researchers recently set out to determine if abnormal intestinal microbiota may in fact be associated with persistent gastrointestinal symptoms in gluten-free celiac disease patients. The research team included Pirjo Wacklin PhD, Pilvi Laurikka, Katri Lindfors PhD, Pekka Collin MD, Teea Salmi MD, Marja-Leena Lähdeaho MD, Päivi Saavalainen PhD, Markku Mäki MD, Jaana Mättö PhD, Kalle Kurppa MD, and Katri Kaukinen MD.
    They are variously associated with the Finnish Red Cross Blood Service, Helsinki, Finland; School of Medicine, University of Tampere, Tampere, Finland; the Tampere Centre for Child Health Research at the University of Tampere and Tampere University Hospital in Tampere, Finland; the Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, in Tampere, Finland; the Department of Dermatology at Tampere University Hospital in Tampere, Finland; the Research Programs Unit of the Immunobiology, and Department of Medical Genetics at the Haartman Institute of the University of Helsinki in Helsinki, Finland; the Department of Internal Medicine at Tampere University Hospital in Tampere, and with Seinäjoki Central Hospital in Seinäjoki, Finland,
    The team used 16S rRNA gene pyrosequencing to analyze duodenal microbiota in 18 gluten-free celiac patients suffering from persistent symptoms, and 18 gluten-free celiac patients without symptoms.
    All celiac patients had been following a strict gluten-free diet for several years, and had restored small bowel mucosa and tested negative for celiac autoantibodies.
    The team rated symptoms using the Gastrointestinal Symptom Rating Scale, and found that gluten-free celiac disease patients with persistent symptoms had different duodenal bacteria than celiac patients without symptoms.
    Gluten-free celiac patients with persistent symptoms had a higher relative abundance of Proteobacteria (P=0.04) and a lower abundance of Bacteroidetes (P=0.01) and Firmicutes (P=0.05). Moreover, they had a much narrower range of bacteria types in their guts.
    The discovery that dysbiosis of microbiota is associated with persistent gastrointestinal symptoms in gluten-free celiac patients offers a new avenue of treatment for such patients.
    Source:
    Am J Gastroenterol. 2014;109(12):1933-1941.

    Jefferson Adams
    How Serious is Incomplete Mucosal Recovery in Celiac Patients?
    Celiac.com 07/15/2015 - Current celiac disease call for a follow-up biopsy taken 1 year after diagnosis to monitor gut recovery. Many celiac patients show incomplete gut recovery at that time, but there’s not much research to help doctors figure out how significant this might be.
    A team of researchers recently investigated associated factors and the significance of imperfect gut recovery in patients in whom the follow-up had been completed. The research team included Henna Pekki, Kalle Kurppa, Markku Mäki, Heini Huhtala, Harri Sievänen, Kaija Laurila, Pekka Collin and Katri Kaukinen.
    They are variously affiliated with the Medical School and the School of Health Sciences at the University of Tampere, the Tampere Center for Child Health Research at the University of Tampere and Tampere University Hospital in Tampere, Finland, the UKK Institute inTampere, Finland, the Department of Gastroenterology and Alimentary Tract Surgery, and the Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.
    For their study, the team split 263 biopsy-proven celiac patients into two groups: one with histological recovery, and the other with incomplete recovery, after one year on gluten-free diet. The team measured serology, laboratory values, bone mineral density, and various clinical variables at diagnosis and after one year.
    They used validated questionnaires to assess gastrointestinal symptoms and quality of life, and also gathered further long-term follow-up data on mortality, malignancies, and other severe complications.
    The results showed that the incomplete recovery group had more severe mucosal damage (P=0.003), higher antibody values (P=0.017), and more signs of malabsorption at diagnosis (P<0.001).
    The data showed no difference in gender, symptoms or quality of life, family history of celiac disease, or co-morbidities.
    Follow-up showed a difference in antibodies (P=0.018) and femoral T-scores (P=0.024).
    Histologically recovered patients showed better gluten-free dietary adherence, although both groups reported close adherence to a gluten-free diet (97% for recovered group, versus 87% for the incomplete group (P<0.001).
    Interestingly, there was no difference in long-term outcomes between groups. Although, patients with more severe celiac disease in terms of histology, serology, and signs of malabsorption were more likely to show histological non-response.
    Patients who closely follow a gluten-free diet, incomplete villous recovery after 1 year does not affect the clinical response or long-term prognosis.

    Source:
    The American Journal of Gastroenterology , (2 June 2015). doi:10.1038/ajg.2015.155

    Jefferson Adams
    Full Gut Recovery from Celiac Disease Can Take Up to Two Years
    Celiac.com 03/14/2017 - Recent studies of adult celiacs have suggested that complete, not just partial, mucosal recovery and healing is possible, but, in many cases, may take longer than is currently understood.
    Recently Dr. Hugh James Freeman of the Department of Medicine, Gastroenterology, University of British Columbia, Vancouver, BC, Canada, conducted a study to assess healing time in celiac patients. In this study, 182 patients (60 males, 122 females) referred for evaluation of symptoms, including diarrhea and weight loss, were selected only if initial biopsies showed characteristic inflammatory changes with severe architectural disturbance.
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    However, celiacs who are diagnosed later, start a gluten-free diet later, and who have inflammatory changes with persistent gut damage may be at increased risk for a later small bowel complication, including lymphoma.
    The overall good news here is that full mucosal healing can and does occur in most people with celiac disease. Some people may take longer to heal, but the evidence shows that most do eventually heal.
    Source:
    International Journal of Celiac Disease, 2017, Vol. 5, No. 1, xx. DOI:10.12691/ijcd-5-1-4

    Jefferson Adams
    Study Shows Non-celiac Wheat Sensitivity is a Persistent Condition
    Celiac.com 08/23/2017 - A team of researchers recently set out to assess how many patients with a diagnosis of non-celiac wheat sensitivity (NCWS) still experienced symptoms of wheat sensitivity after an average follow-up time of 99 months.
    The research team included Antonio Carroccio, Alberto D’Alcamo, Giuseppe Iacono, Maurizio Soresi, Rosario Iacobucci, Andrea Arini, Girolamo Geraci, Francesca Fayer, Francesca Cavataio, Francesco La Blasca, Ada M. Florena, and Pasquale Mansueto.
    Using data collected from 200 participants from a previous study of non-celiac wheat sensitivity, performed between July and December 2016 in Italy, the team found that 148 of these individuals still followed a strict wheat-free diet.
    In total, 175 patients (88%) said that they had fewer symptoms after a diagnosis of non-celiac wheat sensitivity and general improvement.
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    Of the 22 patients who repeated the double-blind, placebo-controlled challenge, 20 reacted to wheat.
    The numbers and percentages of the 148 non-celiac wheat sensitivity patients on a strict wheat-free diet who reported that the following symptoms recurred after occasional and accidental wheat consumption: Lack of well-being 135 (91%); Tiredness 102 (69%); Foggy mind 68 (46%); Menstrual alterations 54 (36%); Anemia 46 (31%); Weight increase 45 (30%); Joint/muscle pain 35 (24%); Headache 31 (21%); Weight loss 30 (20%); Anxiety 18 (12%); Skin rash 16 (11%); Recurrent cystitis 12 (8%); Depression 10 (7%).
    From these numbers, the team concludes that non-celiac wheat sensitivity is a persistent condition.
    Clinicaltrials.gov registration number: NCT02823522.
    Source:
    Gastroenterology. DOI: http://dx.doi.org/10.1053/j.gastro.2017.03.034

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