Dataset Information

Gut microbiota in Celiac Disease: microbes, metabolites, pathways and therapeutics.

ABSTRACT:

Introduction

Current evidence supports a vital role of the microbiota on health outcomes, with alterations in an otherwise healthy balance linked to chronic medical conditions like celiac disease (CD). Recent advances in microbiome analysis allow for unparalleled profiling of the microbes and metabolites. With the growing volume of data available, trends are emerging that support a role for the gut microbiota in CD pathogenesis.

Areas covered

In this article, the authors review the relationship between factors such as genes and antibiotic exposure on CD onset and the intestinal microbiota. The authors also review other microbiota within the human body (like the oropharynx) that may play a role in CD pathogenesis. Finally, the authors discuss implications for disease modification and the ultimate goal of prevention. The authors reviewed literature from PubMed, EMBASE, and Web of Science.

Expert opinion

CD serves as a unique opportunity to explore the role of the intestinal microbiota on the development of chronic autoimmune disease. While research to date provides a solid foundation, most studies have been case-control and thus do not have capacity to explore the mechanistic role of the microbiota in CD onset. Further longitudinal studies and integrated multi-omics are necessary for investigating CD pathogenesis.

SUBMITTER: Olshan KL

PROVIDER: S-EPMC7796936 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Gut microbiota in Celiac Disease: microbes, metabolites, pathways and therapeutics.

Olshan Katherine L KL Leonard Maureen M MM Serena Gloria G Zomorrodi Ali R AR Fasano Alessio A

Expert review of clinical immunology 20201101 11

<h4>Introduction</h4>Current evidence supports a vital role of the microbiota on health outcomes, with alterations in an otherwise healthy balance linked to chronic medical conditions like celiac disease (CD). Recent advances in microbiome analysis allow for unparalleled profiling of the microbes and metabolites. With the growing volume of data available, trends are emerging that support a role for the gut microbiota in CD pathogenesis.<h4>Areas covered</h4>In this article, the authors review th ...[more]

PMID: 33103934

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Project description:IntroductionPotential celiac disease (pCD) is characterized by genetic predisposition, positive anti-endomysial and anti-tissue transglutaminase antibodies, but a normal or almost normal jejunal mucosa (e.g., minor histological abnormalities without villous atrophy). To gain further insights into basic mechanisms involved in the development of intestinal villous atrophy, we evaluated and compared the microbial, lipid, and immunological signatures of pCD and atrophic CD (aCD).Materials and methodsThis study included 17 aCD patients, 10 pCD patients, and 12 healthy controls (HC). Serum samples from all participants were collected to analyze free fatty acids (FFAs). Duodenal mucosa samples of aCD and pCD patients were taken to evaluate histology, tissue microbiota composition, and mucosal immune response.ResultsWe found no significant differences in the mucosa-associated microbiota composition of pCD and aCD patients. On the other hand, in pCD patients, the overall abundance of serum FFAs showed relevant and significant differences in comparison with aCD patients and HC. In detail, compared to HC, pCD patients displayed higher levels of propionic, butyric, valeric, 2-ethylhexanoic, tetradecanoic, hexadecanoic, and octadecanoic acids. Instead, aCD patients showed increased levels of propionic, isohexanoic, and 2-ethylhexanoic acids, and a lower abundance of isovaleric and 2-methylbutyricacids when compared to HC. In addition, compared to aCD patients, pCD patients showed a higher abundance of isobutyric and octadecanoic acid. Finally, the immunological analysis of duodenal biopsy revealed a lower percentage of CD4+ T lymphocytes in pCD infiltrate compared to that observed in aCD patients. The functional characterization of T cells documented a pro-inflammatory immune response in both aCD and pCD patients, but the pCD patients showed a higher percentage of Th0/Th17 and a lower percentage of Th1/Th17.ConclusionThe results of the present study show, for the first time, that the duodenal microbiota of patients with pCD does not differ substantially from that of aCD; however, serum FFAs and local T cells displayed a distinctive profile between pCD, aCD, and HC. In conclusion, our result may help to shed new light on the "gut microbiota-immunity axis," lipid metabolites, and duodenal immune response in overt CD and pCD patients, opening new paradigms in understanding the pathogenesis behind CD progression.

Project description:Celiac disease (CD) is an autoimmune disease caused by a loss of gluten tolerance in genetically predisposed individuals. While 30%-40% of people possess the predisposing alleles, only 1%-2% are diagnosed with CD, suggesting that environmental factors are involved in disease pathogenesis. To determine an association between pediatric CD and the gut microbiome, we analyzed fecal samples from a prospective cohort study (ABIS). These samples were collected from children who later developed CD (CD progressors) and age-matched healthy children (at ages 1, 2.5, and 5) with similar HLA genotypes, breastfeeding durations, and gluten exposure times. We previously reported gut microbiome differences at ages 2.5 and 5 in this cohort; here, we present findings from samples collected at age 1 (n = 5). We identified 14 ASVs differing significantly between CD progressors and controls, including taxa linked to CD pathogenesis. CD progressors had increased Firmicutes and higher alpha diversity in IgA- bacteria. Using PICRUSt, we analyzed metabolic pathways enriched in CD progressors compared to controls at ages 1, 2.5, and 5 (n = 5-16), revealing enriched inflammatory and pathogenic pathways potentially contributing to CD-related immune dysregulation. While results are based on the primary EdgeR analysis, we also applied a non-parametric method of statistical analysis, reporting those results with supplementary figures. In conclusion, our findings suggest distinct metabolic pathways enriched in the gut microbiome of CD progressors years before diagnosis, which could inform targeted therapeutics for CD. As discussed in the limitations section, this small pilot study should be replicated with larger sample sizes for broader generalization.ImportanceWe analyzed gut microbiome data from children who later developed celiac disease (CD progressors) compared to healthy children in the first 5 years of life. Using fecal samples corresponding to the three phases of gut microbiome development, we uncovered enriched functional microbial pathways in CD progressors at age 1. Some of these pathways, implicated in bacterial pathogenesis, microbiota modulation, and inflammation, have been correlated with CD. We also identified taxa in CD progressors at age 1 including Lachnospiraceae, Alistipes, and Bifidobacterium dentium that were previously associated with CD. These findings suggest a potential role for these taxa and enriched pathways in pediatric CD onset years before diagnosis, highlighting potential for early interventions. While the findings of this exploratory study should be validated with larger sample sizes, our study suggests microbial metabolic pathways related to CD onset, enhancing our understanding of CD pathogenesis and the role of gut microbiome-mediated early alterations.

Dataset Information

Gut microbiota in Celiac Disease: microbes, metabolites, pathways and therapeutics.

Introduction

Areas covered

Expert opinion

Publications

Gut microbiota in Celiac Disease: microbes, metabolites, pathways and therapeutics.

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