The abundance of Akkermansia muciniphila and its relationship with sulphated colonic mucins in health and ulcerative colitis

Helen Earley,Desmond C Winter,J Calvin Coffey,Grainne Lennon,P Ronan O'Connell,Áine Balfe

doi:10.1038/s41598-019-51878-3

Abstract

Akkermansia muciniphila utilises colonic mucin as its substrate. Abundance is reduced in ulcerative colitis (UC), as is the relative proportion of sulphated mucin in the mucus gel layer (MGL). It is unknown if these phenomena are related, however reduced sulphated mucins could contribute to reduced abundance, owing to a lack of substrate. The aim of this study was to quantify A. muciniphila within the MGL and to relate these findings with markers of inflammation and the relative proportion of sulphomucin present. Colonic biopsies and mucus brushings were obtained from 20 patients with active UC (AC), 14 with quiescent UC (QUC) and 20 healthy controls (HC). A. muciniphila abundance was determined by RT-PCR. High iron diamine alcian-blue staining was performed for histological analysis. Patients with AC had reduced abundance of A. muciniphila compared to HC and QUC. A positive association was found between A. muciniphila abundance and higher percentage of sulphated mucin (ρ 0.546, p = 0.000). Lower abundances of A. muciniphila correlated with higher inflammatory scores (ρ = 0.294 (p = 0.001)). This study confirms an inverse relationship between A. muciniphila and inflammation and a positive association between A. muciniphila abundance and percentage of sulfated mucin in the MGL.

Highlights

Akkermansia muciniphila utilises colonic mucin as its substrate
Subsequent inter-cohort statistical analysis was performed based on the Mann Whitney U test, revealing a reduction in total bacterial copy numbers in active UC (AC) compared to healthy controls (HC) (Fig. 2a, Table 1.) A significant reduction was observed in AC compared to quiescent UC (QUC)
A. muciniphila has been widely detected in faecal samples and mucosal biopsies[1,3,26], to the authors’ knowledge, this is the first study to quantitatively analyse this species in mucus brushings of the colonic mucus

Summary

Introduction

Abundance is reduced in ulcerative colitis (UC), as is the relative proportion of sulphated mucin in the mucus gel layer (MGL). The mucus gel layer (MGL), comprised predominantly of mucins, represents the host microbial interface in the human colon. It is composed of a loosely adherent outer layer, which is home to the resident microbiota and a densely adherent inner layer which prevent bacterial penetration to the epithelium[13]. Quantitative and qualitative changes occur within the MGL in UC, including depletion of the layer, altered glycosylation and alterations of the proportions of sulphated and sialyated mucin[14,15,16] Such changes alter the microenvironment in which the commensal microbiota resides, which may have implications for their survival. A degree of spatial variation exists across the cross sectional axis of the human colon, with distinct microbial communities residing in the luminal contents, mucus and mucosa[18,19,20]

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