Proximal Small Intestinal Microbiota and Identification of Rod-Shaped Bacteria Associated With Childhood Celiac Disease

Ou, Gangwei; Hedberg, Maria; Hörstedt, Per; Baranov, Vladimir; Forsberg, Göte; Drobni, Mirva; Sandström, Olof; Wai, Sun Nyunt; Johansson, Ingegerd; Hammarström, Marie‐Louise; Hernell, Olle; Hammarström, Sten

doi:10.1038/ajg.2009.524

Cited by 142 publications

(127 citation statements)

References 28 publications

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“…9 It has been proposed that some immunologically relevant CD-associated alleles-including the SH2B3 rs3184504*A allele, which plays a protective role against bacterial infection-may have undergone positive selection rather recently. 8 This finding, along with those in other recent studies of the role of infections 10 and intestinal indigenous microflora composition 11,12 in CD, show that immune reactions to gluten are strongly influenced by changes in the intestinal microbiome.…”

supporting

confidence: 78%

Celiac disease: a model disease for gene–environment interaction

2011

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supporting

confidence: 78%

Celiac disease: a model disease for gene–environment interaction

2011

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“…In recent T1D and CD investigations, intestinal microbiota have received attention as possible modulators of disease development. [27][28][29][30] However, one could ask whether the detection of serum antibodies against antigens of a particular commensal bacteria reflects its presence and involvement in immune reactions at the intestinal level. Although it is possible that we detected antibodies induced by antigens that originated from other microorganisms, we are still confident that a portion of the detected antibodies was directed against B. adolescentis itself or other Bifidobacterium spp.…”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24] In experimentally induced diabetes in rats or mice, changes in intestinal permeability are also detected before the onset of diabetes; increased intestinal permeability in these cases has been shown to be dependent on increased zonulin expression, which regulates tight junctions in the intestinal mucosa. [25][26][27] Additionally, mucosal biopsy, fecal microbiota and serological studies have indicated that the composition of intestinal microbiota may influence the immune mechanisms that participate in the development of CD 28,29 and T1D. 27,29,30 Consistent with these studies, recent investigations have stressed the importance of Bifidobacteria species and strains in the modulation of immune reactivity at the intestinal mucosa level.…”

Section: Introductionmentioning

confidence: 92%

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

et al. 2011

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Two common chronic childhood diseases-celiac disease (CD) and type 1 diabetes (T1D)-result from complex pathological mechanisms where genetic susceptibility, environmental exposure, alterations in intestinal permeability and immune responses play central roles. In this study, we investigated whether these characteristics were universal for CD independently of T1D association. For this purpose, we studied 36 children with normal small-bowel mucosa and 26 children with active CD, including 12 patients with T1D. In samples from the small-bowel mucosa, we detected the lowest expression of tight junction protein 1 (TJP1) mRNA in CD patients with T1D, indicating an increase in intestinal permeability. Furthermore, these samples displayed the highest expression of forkhead box P3 (FoxP3) mRNA, a marker for regulatory T cells, as compared with other patient groups. At the same time, serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase (tTG) were the highest in CD patients with T1D. In contrast, no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins. There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals. Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability, strong local immune activation and increased immunoregulatory mechanisms in the small bowel. Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors (virus infections), unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions. INTRODUCTIONWith an approximate prevalence of 1.0% in Western countries, celiac disease (CD) is one of the most common lifelong chronic disorders. 1 CD and type 1 diabetes (T1D) form a significant sector of childhood diseases with high rate of co-occurrence. 2 Both diseases are autoimmune in origin and develop as a result of complex pathological mechanisms, involving several common genetic, environmental and immunological factors. Among these, the common susceptibility loci of HLA and other immune system-related genes, 3 permeability changes in the small-bowel mucosa, 4 and association with wheat consumption 4,5 are prominent. Both diseases are increasing in most regions of the world, 6,7 as are several other autoimmune diseases, but the actual cause of the disease remains unknown. However, several recent studies have highlighted the role of environmental and social changes that have taken place over the last several decades. 8,9 The central event in the pathogenesis of CD is damage to the small intestinal mucosa that occurs after ingestion of gluten or related prolamins in genetically susceptible individuals. During this process, several morphological and immunological alterations have been demonstrated in the small-bowel mucos...

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“…Carcinoembryonic antigen-related cell adhesion molecule (CEACAM), one member of CEA gene family, belongs to the immunoglobulin superfamily of adhesion molecule anchoring at the cell membrane. CEACAM1 is considered to be anti-oncogene, but expressing in lung cancer, especially in lung adenocarcinoma, can promote tumor angiogenesis (Ou et al, 2009). CEACAM5 and CEACAM6 are considered to be oncogene.…”

Section: Discussionmentioning

confidence: 99%