Gut microbiota trajectory in early life may predict development of celiac disease

Marta Olivares,Francesc Palau,Julian Parkhill,Amalia Capilla,Gemma Castillejo,Alan W Walker,Yolanda Sanz,Alfonso Benítez-Páez

doi:10.1186/s40168-018-0415-6

Abstract

BackgroundTo investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease (CD) onset in infants at familial risk of developing the disease.MethodsA nested case-control study was carried out as part of a larger prospective cohort study, which included healthy full-term newborns (> 200) with at least one first relative with biopsy-verified CD. The present study includes cases of CD (n = 10) and the best-matched controls (n = 10) who did not develop the disease after 5-year follow-up. Fecal microbiota, assessed by high-throughput 16S rRNA gene amplicon sequencing, and immune parameters were profiled at 4 and 6 months of age and related to CD onset.ResultsThe microbiota of infants who remained healthy showed an increase in bacterial diversity over time, characterized by increases in Firmicutes families, but not those who developed CD. Infants who subsequently developed CD showed a significant reduction in sIgA levels over time, while those who remained healthy showed increases in TNF-α correlated to Bifidobacterium spp. An increased relative abundance of Bifidobacterium longum was associated with control children while increased proportions of Bifidobacterium breve and Enterococcus spp. were associated with CD development.ConclusionThe findings suggest that alterations in the early trajectory of gut microbiota in infants at CD risk could influence the immune maturation process and predispose to CD, although larger population studies are warranted to confirm this hypothesis.

Highlights

To investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease (CD) onset in infants at familial risk of developing the disease
Celiac disease (CD) is an immune-mediated systemic disorder elicited by an aberrant response to dietary gluten proteins found in wheat, rye, and barley, which develops in genetically predisposed individuals [1]
Demographic data, genetics, and early feeding pattern of the infants A nested case-control study was conducted to investigate the role of the evolution of the infant gut microbiota in CD onset in a subset of subjects selected from a larger prospective cohort study [23]

Summary

Introduction

To investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease (CD) onset in infants at familial risk of developing the disease. Celiac disease (CD) is an immune-mediated systemic disorder elicited by an aberrant response to dietary gluten proteins found in wheat, rye, and barley, which develops in genetically predisposed individuals [1]. 30–40% of the Caucasian subjects carry these risk haplotypes but most of them do not develop the disease, Gluten intake is the only environmental trigger of CD with an established pathogenic role. APCs recognize gluten peptides and activate lamina propria infiltrating T lymphocytes. This leads to the release of pro-inflammatory cytokines, mainly interferon (IFN)γ and IL-15, activation of cytotoxic T cells, and profound tissue damage [6, 7].

Objectives

Methods

Results

Discussion

Conclusion