Comparison of Small Gut and Whole Gut Microbiota of First-Degree Relatives With Adult Celiac Disease Patients and Controls.

Rahul Bodkhe,Sudarshan A Shetty,Asha Mishra,Govind K Makharia,Rajadurai C Perumal,Anil K Verma,Pranav Pande,Dhiraj P Dhotre,Beena P Santosh,Vineet Ahuja,Gurvinder Kaur,Khushbo Bhatia,Dhinoth K Bangarusamy,Yogesh S Shouche

doi:10.3389/fmicb.2019.00164

Abstract

Recent studies on celiac disease (CeD) have reported alterations in the gut microbiome. Whether this alteration in the microbial community is the cause or effect of the disease is not well understood, especially in adult onset of disease. The first-degree relatives (FDRs) of CeD patients may provide an opportunity to study gut microbiome in pre-disease state as FDRs are genetically susceptible to CeD. By using 16S rRNA gene sequencing, we observed that ecosystem level diversity measures were not significantly different between the disease condition (CeD), pre-disease (FDR) and control subjects. However, differences were observed at the level of amplicon sequence variant (ASV), suggesting alterations in specific ASVs between pre-disease and diseased condition. Duodenal biopsies showed higher differences in ASVs compared to fecal samples indicating larger disruption of the microbiota at the disease site. The duodenal microbiota of FDR was characterized by significant abundance of ASVs belonging to Parvimonas, Granulicatella, Gemella, Bifidobacterium, Anaerostipes, and Actinomyces genera. The duodenal microbiota of CeD was characterized by higher abundance of ASVs from genera Megasphaera and Helicobacter compared to the FDR microbiota. The CeD and FDR fecal microbiota had reduced abundance of ASVs classified as Akkermansia and Dorea when compared to control group microbiota. In addition, predicted functional metagenome showed reduced ability of gluten degradation by CeD fecal microbiota in comparison to FDRs and controls. The findings of the present study demonstrate differences in ASVs and predicts reduced ability of CeD fecal microbiota to degrade gluten compared to the FDR fecal microbiota. Further research is required to investigate the strain level and active functional profiles of FDR and CeD microbiota to better understand the role of gut microbiome in pathophysiology of CeD.

Highlights

Celiac disease is a common, chronic immune mediated enteropathy of the small intestine which affects approximately 0.7% of the global population (Singh et al, 2018)
At the phylum level there was no significant difference in the abundance of Firmicutes, the order Clostridiales within this phylum showed significantly higher abundance in first degree relatives (FDR) microbiota compared to diseased controls (DC) microbiota (p < 0.05) (Supplementary Figure S2)
There was no significant difference in abundance of the other major phyla between the FDR and celiac disease (CeD) as well as the CeD and DC microbiota (Figure 2)

Summary

Introduction

Celiac disease is a common, chronic immune mediated enteropathy of the small intestine which affects approximately 0.7% of the global population (Singh et al, 2018). The prevalence of CeD has been on the rise, especially in developing countries (Lohi et al, 2007). This rapid rise in disease prevalence cannot be attributed only to the underlying genetic makeup of the population but rather to the environmental factors including infant feeding practices, reduction in infectious diseases, reovirus infection, and use of antibiotics (Jabri and Sollid, 2006; Lohi et al, 2007; Myléus et al, 2009; Volta and De Giorgio, 2012; Mårild et al, 2013; Bouziat et al, 2017). There remains a possibility that enzymes secreted by the small intestinal microbiota convert some of these immunogenic peptides to non-immunogenic peptides

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