Pirjo Wacklin1, Pilvi Laurikka2, Katri Lindfors3, Pekka Collin4, Teea Salmi5, Marja-Leena Lähdeaho3, Päivi Saavalainen6, Markku Mäki3, Jaana Mättö1, Kalle Kurppa3, Katri Kaukinen7. 1. Finnish Red Cross Blood Service, Helsinki, Finland. 2. School of Medicine, University of Tampere, Tampere, Finland. 3. Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland. 4. 1] School of Medicine, University of Tampere, Tampere, Finland [2] Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland. 5. 1] School of Medicine, University of Tampere, Tampere, Finland [2] Department of Dermatology, Tampere University Hospital, Tampere, Finland. 6. Research Programs Unit, Immunobiology, and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland. 7. 1] School of Medicine, University of Tampere, Tampere, Finland [2] Department of Internal Medicine, Tampere University Hospital, Tampere and Seinäjoki Central Hospital, Seinäjoki, Finland.
Abstract
OBJECTIVES: A significant fraction of celiac disease patients suffer from persistent symptoms despite a long-term gluten-free diet (GFD) and normalized small bowel mucosa. The commonly suggested reasons, such as inadvertent gluten-intake or presence of other gastrointestinal disease, do not explain the symptoms in all these patients. Recently, alterations in intestinal microbiota have been associated with autoimmune disorders, including celiac disease. This led us to test a hypothesis that abnormal intestinal microbiota may be associated with persisting gastrointestinal symptoms in treated celiac disease patients. METHODS: Duodenal microbiota was analyzed in 18 GFD-treated patients suffering from persistent symptoms and 18 treated patients without symptoms by 16S rRNA gene pyrosequencing. The celiac disease patients had been following a strict GFD for several years and had restored small bowel mucosa and negative celiac autoantibodies. Their symptoms on GFD were assessed with Gastrointestinal Symptom Rating Scale. RESULTS: The results of several clustering methods showed that the treated celiac disease patients with persistent symptoms were colonized by different duodenal microbiota in comparison with patients without symptoms. The treated 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, their microbial richness was reduced. The results indicated intestinal dysbiosis in patients with persistent symptoms even while adhering to a strict GFD. CONCLUSIONS: Our findings indicate that dysbiosis of microbiota is associated with persistent gastrointestinal symptoms in treated celiac disease patients and open new possibilities to treat this subgroup of patients.
OBJECTIVES: A significant fraction of celiac diseasepatients suffer from persistent symptoms despite a long-term gluten-free diet (GFD) and normalized small bowel mucosa. The commonly suggested reasons, such as inadvertent gluten-intake or presence of other gastrointestinal disease, do not explain the symptoms in all these patients. Recently, alterations in intestinal microbiota have been associated with autoimmune disorders, including celiac disease. This led us to test a hypothesis that abnormal intestinal microbiota may be associated with persisting gastrointestinal symptoms in treated celiac diseasepatients. METHODS: Duodenal microbiota was analyzed in 18 GFD-treated patients suffering from persistent symptoms and 18 treated patients without symptoms by 16S rRNA gene pyrosequencing. The celiac diseasepatients had been following a strict GFD for several years and had restored small bowel mucosa and negative celiac autoantibodies. Their symptoms on GFD were assessed with Gastrointestinal Symptom Rating Scale. RESULTS: The results of several clustering methods showed that the treated celiac diseasepatients with persistent symptoms were colonized by different duodenal microbiota in comparison with patients without symptoms. The treated 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, their microbial richness was reduced. The results indicated intestinal dysbiosis in patients with persistent symptoms even while adhering to a strict GFD. CONCLUSIONS: Our findings indicate that dysbiosis of microbiota is associated with persistent gastrointestinal symptoms in treated celiac diseasepatients and open new possibilities to treat this subgroup of patients.