Finnish Red Cross Blood Service, Helsinki, Finland.
School of Medicine, University of Tampere, Tampere, Finland.
Am J Gastroenterol. 2014 Dec;109(12):1933-41. doi: 10.1038/ajg.2014.355. Epub 2014 Nov 18.
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.
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.
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.
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.
尽管长期遵循无麸质饮食（GFD）且小肠黏膜已恢复正常，但仍有相当一部分乳糜泻患者存在持续性症状。通常认为，这些患者的症状无法通过偶然摄入麸质或存在其他胃肠道疾病来解释。最近，肠道微生物群的改变与包括乳糜泻在内的自身免疫性疾病有关。这使我们产生了一个假设，即异常的肠道微生物群可能与接受治疗的乳糜泻患者持续存在的胃肠道症状有关。
通过 16S rRNA 基因焦磷酸测序分析 18 例持续性症状的 GFD 治疗乳糜泻患者和 18 例无症状治疗乳糜泻患者的十二指肠微生物群。这些乳糜泻患者已遵循严格的 GFD 多年，且已恢复小肠黏膜并出现阴性乳糜泻自身抗体。他们的 GFD 症状通过胃肠道症状评分量表进行评估。
几种聚类方法的结果表明，与无症状患者相比，持续性症状的治疗后乳糜泻患者的十二指肠菌群定植不同。持续性症状的治疗患者中，变形菌（Proteobacteria）的相对丰度更高（P=0.04），拟杆菌门（Bacteroidetes）和厚壁菌门（Firmicutes）的丰度更低（P=0.01 和 P=0.05）。此外，他们的微生物丰富度降低。即使坚持严格的 GFD，持续性症状患者的肠道菌群失调也表明存在这种情况。
我们的研究结果表明，微生物群的失调与接受治疗的乳糜泻患者持续性胃肠道症状有关，并为治疗该亚组患者开辟了新的可能性。
