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The correlation between fecal microbiota profiles and intracellular junction genes expression in young Iranian
Mohadeseh Mahmoudi Ghehsareh1, Nastaran Asri2, Fahimeh Sadat Gholam-Mostafaei3
1Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medica lSciences, Islamic Azad University, Tehran, Iran.
Insights
Celiac disease (CD) alters gut microbiota and intestinal barrier genes. Pediatric CD patients show distinct microbial profiles and changes in tight junction gene expression, particularly ZO-1 and beta-catenin.
Area of Science:
- Gastroenterology
- Microbiology
- Immunology
Background:
- Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion, leading to intestinal inflammation and barrier dysfunction.
- Alterations in gut microbiota composition are increasingly recognized as a contributing factor in CD pathogenesis.
- Understanding the interplay between microbiota and intestinal barrier integrity is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate changes in fecal microbiota and mRNA expression of intracellular junction-related genes in pediatric celiac disease patients.
- To compare microbial profiles and gene expression between active CD, treated CD, and healthy controls (HCs).
- To explore potential correlations between specific microbial taxa and intestinal barrier gene expression in CD.
Main Methods:
- Quantitative real-time PCR (qPCR) was used to analyze fecal microbiota composition and mRNA expression of ZO-1, occludin, β-catenin, E-cadherin, and COX-2.
- Peripheral blood samples were collected for gene expression analysis.
- A cohort of 30 treated CD patients, 10 active CD patients, and 40 HCs were included in the study.
Main Results:
- Active and treated CD patients exhibited lower peripheral blood (PB) expression of ZO-1 and β-catenin compared to HCs.
- PB Occludin levels were upregulated in both active and treated CD patients versus HCs.
- Active CD patients showed a higher relative abundance of Firmicutes and Actinobacteria phyla, and lower relative abundance of Veillonella and Staphylococcus genera compared to treated subjects or HCs.
Conclusions:
- Pediatric celiac disease is associated with significant alterations in gut microbiota composition and peripheral blood expression of tight junction-related genes.
- Specific microbial shifts, including increased Firmicutes and Actinobacteria, are observed in active CD.
- Further research is warranted to elucidate the precise impact of the gut microbiome on intestinal damage mechanisms in CD, with a focus on Bifidobacteria and Enterobacteriaceae.
Abstract:
Celiac disease (CD) is characterized by the disruption of the intestinal barrier integrity and alterations in the microbiota composition. This study aimed to evaluate the changes in the fecal microbiota profile and mRNA expressions of intracellular junction-related genes in pediatric patients with CD compared to healthy controls (HCs). Thirty treated CD patients, 10 active CD, and 40 HCs were recruited. Peripheral blood (PB) and fecal samples were collected. Microbiota analysis was performed using quantitative real-time PCR (qPCR) test. The mRNA expressions of ZO-1, occludin, β-catenin, E-cadherin, and COX-2 were also evaluated. In active and treated CD patients, the PB expression levels of ZO-1 (p = 0.04 and 0.002, respectively) and β-catenin (p = 0.006 and 0.02, respectively) were lower than in HCs. PB Occludin's level was upregulated in both active and treated CD patients compared to HCs (p = 0.04 and 0.02, respectively). However, PB E-cadherin and COX-2 expression levels and fecal mRNA expressions of ZO-1, occludin, and COX-2 did not differ significantly between cases and HCs (P˃0.05). Active CD patients had a higher relative abundance of the Firmicutes (p = 0.04) and Actinobacteria (p = 0.03) phyla compared to treated subjects. The relative abundance of Veillonella (p = 0.04) and Staphylococcus (p = 0.01) genera was lower in active patients in comparison to HCs. Researchers should explore the precise impact of the gut microbiome on the molecules and mechanisms involved in intestinal damage of CD. Special attention should be given to Bifidobacteria and Enterobacteriaceae, as they have shown a significant correlation with the expression of tight junction-related genes.
