*Finnish Red Cross Blood Service, Helsinki, Finland †Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland ‡Pediatric Research Center, Tampere University Hospital, University of Tampere, Tampere, Finland.
Celiac disease is classically manifested in the gastrointestinal (GI) tract but extraintestinal symptoms, such as dermatitis herpetiformis (DH), are also common. Besides several well-known shared genetic risk factors and an environmental trigger, gliadin, factors determining the clinical outcome of the disease are not known. In this study, the role of duodenal microbiota in the celiac disease outcome was studied by analyzing mucosa-associated microbiota in celiac disease patients with a variety of intestinal and extraintestinal symptoms.
Microbiota in duodenal biopsy samples obtained from 33 patients with celiac disease with GI, DH, anemia, or mixed symptoms, as well as screen-detected asymptomatic celiac disease and 18 control subjects were analyzed using PCR denaturing gradient gel electrophoresis and a subset of samples additionally by the 16S ribosomal RNA gene sequencing.
The composition and diversity of mucosal microbiota was associated with the manifestation of celiac disease when analyzed using PCR denaturing gradient gel electrophoresis and the 16S ribosomal RNA gene sequencing. The patients with celiac disease with GI symptoms or anemia had lower microbial diversity than those with DH. Moreover, the patients with GI symptoms had different intestinal microbiota composition and structure, dominated by Proteobacteria, in comparison to those with DH or control subjects (patients with dyspepsia). The relatively similar intestinal microbiota composition in the control subjects and those with DH was characterized by the high abundance of Firmicutes.
The two common outcomes of celiac disease, classical GI and extraintestinal manifestations, had marked differences on the diversity and composition of intestinal microbiota. This association suggested that intestinal microbiota may have a role in the manifestation of the disease.
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"Thus far, there does not appear to be a uniform " CD microbiome " to be found from these studies, with complicating factors being the variations in anatomical location from which samples were acquired, experimental methodology, and the inherent heterogeneity found in CD. In fact, one study has highlighted the differences that are found in patients depending on the presence of extraintestinal symptoms , while others have demonstrated differences between active CD patients and patients on a gluten free diet . Below we discuss how having a dysregulated microbiome can aid in reaching the threshold necessary to develop CD. "
"(Metalloproteases are virulence factors: enterotoxins associated with diarrhoea in human subjects and associated with alterations of tight junctions and inflammation in a murine model.)( 155
) Increased numbers of staphylococci and enterobacteria have been shown in patients with active disease, with numbers restored after adherence to a gluten-free diet(
), but an increased abundance of Staphylococcus epidermidis strains carrying a methicillin-resistance gene has been observed in patients with active and inactive disease(
). Furthermore, virulent clones of E. coli harboured increased virulence factors, for example, haemolysin, P fimbriae and capsule K5, making them more successful as pathogens. "
[Show abstract][Hide abstract] ABSTRACT: The present report describes the presentations delivered at the 7th International Yakult Symposium, 'The Intestinal Microbiota and Probiotics: Exploiting Their Influence on Health', in London on 22-23 April 2013. The following two themes associated with health risks were covered: (1) the impact of age and diet on the gut microbiota and (2) the gut microbiota's interaction with the host. The strong influence of the maternal gut microbiota on neonatal colonisation was reported, as well as rapid changes in the gut microbiome of older people who move from community living to residential care. The effects of dietary changes on gut metabolism were described and the potential influence of inter-individual microbiota differences was noted, in particular the presence/absence of keystone species involved in butyrate metabolism. Several speakers highlighted the association between certain metabolic disorders and imbalanced or less diverse microbiota. Data from metagenomic analyses and novel techniques (including an ex vivo human mucosa model) provided new insights into the microbiota's influence on coeliac, obesity-related and inflammatory diseases, as well as the potential of probiotics. Akkermansia muciniphila and Faecalibacterium prausnitzii were suggested as targets for intervention. Host-microbiota interactions were explored in the context of gut barrier function, pathogenic bacteria recognition, and the ability of the immune system to induce either tolerogenic or inflammatory responses. There was speculation that the gut microbiota should be considered a separate organ, and whether analysis of an individual's microbiota could be useful in identifying their disease risk and/or therapy; however, more research is needed into specific diseases, different population groups and microbial interventions including probiotics.
British Journal Of Nutrition 07/2014; 112 Suppl 1(Suppl 1):S1-S18. DOI:10.1017/S0007114514001275 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The human gut is a unique organ in which hundreds of different microbial species find their habitat and in which different host physiologic functions, such as digestion, nutrition, and immunity, coexist. Although all these players were studied separately for decades, recently, there has been an explosion of studies demonstrating the essential role for interactions between these components in gut function. Furthermore, new systems biology methods provide essential tools to study this complex system as a whole and to identify key elements that define the crosstalk between the gut microbiota, immunity, and metabolism. This review is devoted to several human diseases resulting from the disruption in this crosstalk, including immunodeficiency-associated and environmental enteropathies, celiac disease, inflammatory bowel disease, and obesity. We describe findings in experimental models of these diseases and in germ-free animals that help us understand the mechanisms and test new therapeutic strategies. We also discuss current challenges that the field is facing and propose that a new generation of antibiotics, prebiotics, and probiotics coupled with novel, systems biology-driven diagnostics will provide the basis for future personalized therapy.
The Journal of allergy and clinical immunology 08/2013; 132(2):253-62. DOI:10.1016/j.jaci.2013.06.025 · 11.48 Impact Factor