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.

KEYWORDS:

• Celiac disease
• dysbiosis
• gluten
• gut
• microbiome
• microbiota

Article highlights

• Celiac disease (CD) is a lifelong autoimmune condition in genetically susceptible individuals caused by a sensitivity to dietary gluten. Disease onset can occur at any age.

• The gut microbiome likely plays an important role in CD onset.

• The oropharyngeal, breast milk and blood microbiota are distinct from the gut microbiota, and also likely play important roles in CD onset.

• Genetics and environmental factors, such as antibiotic use and nutrition, heavily influence the composition of the gut microbiome.

• Many tools aimed at manipulating the microbiota, including probiotics and gluten-degrading enzymes, are currently being investigated in the context of CD.

A multi-omics approach and longitudinal studies are necessary to further understand the role of the gut microbiota in CD pathogenesis.

Declaration of interest

A Fasano is a stockholder at Alba Therapeutics, serves as a consultant for Inova Diagnostics and Innovate Biopharmaceuticals, is an advisory board member for Axial Biotherapeutics and Ubiome, and has a speaker agreement with Mead Johnson Nutrition. MM Leonard serves as a consultant to Anokion, has a speaker agreement with Takeda Pharmaceuticals, and performs sponsored research with Glutenostics LLC. All other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was partially supported by funding from the NIH NIDDK; DK104344 to AF and K23DK122127 to MML.This work was partially supported by funding from the NIH NIDDK; DK104344 to A Fasano and K23DK122127 to MM Leonard.