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Objective Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD. Design As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR. Results Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium). Conclusions The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.
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... The genotype of infants at familial risk for CD influences the composition of the early gut microbiota Olivares [25] Infants genetically predisposed to CD show different gut microbiota composition (i.e., prevalence of Bacteroides) ...
... It is important to highlight that, according to several prospective data, HLA-DQ haplotypes affect the composition of the early gut microbiota. Olivares et al. [25], in their prospective study of 22 exclusively breastfed and vaginally delivered children who were either at high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) for CD occurrence, found that the genotype of infants at familial risk for CD, who carry the HLA-DQ2 haplotype, influences the composition of the early gut microbiota, which could help determine the risk of CD. Similarly, other studies also reported a different gut microbiota composition (i.e., prevalence of Bacteroides species associated with intestinal inflammation) in high risk infants for the developmentof CD [26,27]. ...
... In details, the genetic risk to develop CD has been reported to be associated with a decreased abundance of several species of Streptococcus and Coprococcus at 4-6 months of age compared to those lacking genetic compatibility. The authors also reported that standard and high genetic risk for CD occurrence are associated with increased Bacteroides and Enterococcus species compared to no genetic risk, which is in line with previous data [25,27]; conversely, an association between genetic risk and an elevated amount of Bifidobacterium or Proteobacteria, already reported [25,27] was not found. Moreover, a decreased abundance of Veillonella, Parabacteroides, and Clostridium perfringens at 4-6 months after birth in infants with genetic compatibility was observed. ...
Article
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Celiac disease (CD) is a common systemic disorder that results from an abnormal response of human immunity to gluten intake, affecting the small intestine. In individuals who carry a genetic susceptibility, CD is triggered by environmental factors, including viral infections and dysbiosis of the gut microbiota. The gut microbiome is essential in controlling the immune system, and recent findings indicate that changes in the gut microbiome may contribute to various chronic immune disorders, such as CD through mechanisms that still require further exploration. Some bacteria exhibit epitopes that mimic gliadin and may enhance an immune response in the host. Other bacteria, including Pseudomonas aeruginosa, may work in conjunction with gluten to trigger and escalate intestinal inflammation. The microbiota may also directly influence antigen development through the production of immunogenic or tolerogenic gluten peptides or directly influence intestinal permeability through the release of zonulin. Finally, the gut microbiome can impact intestinal inflammation by generating proinflammatory or anti-inflammatory cytokines and metabolites. It is crucial to consider the impact of genetic factors (specifically, HLA-DQ haplotypes), perinatal elements such as birth mode, type of infant feeding, and antibiotic and infection exposure on the composition of the early intestinal microbiome. According to the available studies, the gut microbiome alterations associated with CD tend to exhibit a decreased presence of beneficial bacteria, including some anti-inflammatory Bifidobacterium species. However, some controversy remains as some reports have found no significant differences between the gut microbiomes of individuals with and without CD. A better understanding of the gut microbiome’s role in the development of CD would greatly benefit both prevention and treatment efforts, especially in complicated or treatment-resistant cases. Here, we have attempted to summarize the available evidence on the relationship between the gut microbiota and CD, with a particular focus on potential therapeutic targets.
... What is interesting, it seems that the HLA genotype impacts gut colonization (149). Herein, Olivares et al. observed in a cohort of healthy infants with at least one first-degree relative with CD, that infants carrying the HLA-DQ-2 haplotype have different microbiota composition than non-HLA-DQ-2/8-carriers. Children with a high risk of CD had increased Firmicutes and Proteobacteria proportions but reduced Actinobacteria proportions compared to those with low genetic risk (150). HLA-DQ-2 carriers had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium, unclassified . ...
... proportions (150). On the other hand, gut microbiota alterations seem to contribute to the development of CD (108). ...
Article
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The prevalence of celiac disease increased in recent years. In addition to the genetic and immunological factors, it appears that environmental determinants are also involved in the pathophysiology of celiac disease. Gastrointestinal infections impact the development of celiac disease. Current research does not directly confirm the protective effect of natural childbirth and breastfeeding on celiac disease. However, it seems that in genetically predisposed children, the amount of gluten introduced into the diet may have an impact on celiac disease development. Also western lifestyle, including western dietary patterns high in fat, sugar, and gliadin, potentially may increase the risk of celiac disease due to changes in intestinal microbiota, intestinal permeability, or mucosal inflammation. Further research is needed to expand the knowledge of the relationship between environmental factors and the development of celiac disease to define evidence-based preventive interventions against the development of celiac disease. The manuscript summarizes current knowledge on factors predisposing to the development of celiac disease including factors associated with the western lifestyle.
... SERT is not only present in the brain, it is also widely expressed on epithelial cells of the intestinal mucosa where it removes 5- (Kim et al. 2012;Raman et al. 2013;Schubert et al. 2014) Clostridium sensu stricto 1 ↑ in infants with high genetic risk of developing CD. ↑ in infants with IgE-mediated FA (Ling et al. 2014;Olivares et al. 2014) Intestinibacter ↓ in metformin therapy in patients with T2D (Forslund et al. 2015;Wu et al. 2017) Eubacterium coprostanoligenes Cholesterol-lowering effects (Freier et al. 1994;Li et al. 1998;Li et al. 1995;Ren et al. 1996) Christensenellaceae Rath et al., 1996) Prevotella 7 Prevotella 9 ...
... The characterization of mucosal bacteria in colorectal cancer patients revealed that the alterations in microbial communities related to adenomas may exacerbate the colorectal cancer [46]. The relationship between microbiota composition and host genetics was correlated with coeliac disease development, in which an altered microbiota composition was observed together with the increased expression of leukocyte antigen DQ2 in coeliac disease children [47]. However, the consistent pattern or feature of bacteria alterations in these diseases has not been concluded. ...
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... For example, it is known that enteric infections can cause anxiety, depression, and cognitive dysfunction (181). Taking into account that all aforementioned diseases have a direct or indirect relationship with GM dysbiosis, it is perhaps no coincidence that gut disorders including IBD an IBS are common comorbidities of other disorders such as depression and anxiety (182,183). ...
Thesis
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