Abstract

Genetic haemochromatosis (GH) is responsible for iron overload. Increased transferrin saturation (TSAT) has been associated with severe periodontitis, which is a chronic inflammatory disease affecting tissues surrounding the teeth and is related to dysbiosis of the subgingival microbiota. Because iron is essential for bacterial pathogens, alterations in iron homeostasis can drive dysbiosis. To unravel the relationships between serum iron biomarkers and the subgingival microbiota, we analysed samples from 66 GH patients. The co-occurrence analysis of the microbiota showed very different patterns according to TSAT. Healthy and periopathogenic bacterial clusters were found to compete in patients with normal TSAT (≤45%). However, significant correlations were found between TSAT and the proportions of Porphyromonas and Treponema, which are two genera that contain well-known periopathogenic species. In patients with high TSAT, the bacterial clusters exhibited no mutual exclusion. Increased iron bioavailability worsened periodontitis and promoted periopathogenic bacteria, such as Treponema. The radical changes in host-bacteria relationships and bacterial co-occurrence patterns according to the TSAT level also suggested a shift in the bacterial iron supply from transferrin to NTBI when TSAT exceeded 45%. Taken together, these results indicate that iron bioavailability in biological fluids is part of the equilibrium between the host and its microbiota.

Highlights

  • Periodontitis is a chronic inflammatory disease that affects tissues surrounding the teeth

  • Systemic iron metabolism is controlled by hepcidin, whose expression level is adapted to Transferrin saturation (TSAT) to regulate the plasma iron levels

  • We hypothesized that the alteration of iron metabolism induced by the HFE C282Y gene mutation could modify and drive the subgingival microbiota towards dysbiosis, which could participate in the periodontitis severity

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Summary

Introduction

Periodontitis is a chronic inflammatory disease that affects tissues surrounding the teeth. It is strongly associated with the major pathogenic “red complex”, including Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola[1] and is considered an infection. When TSAT exceeds 45%, non-transferrin-bound iron (NTBI), which is an abnormal biochemical form of iron, occurs in the plasma. We hypothesized that the alteration of iron metabolism induced by the HFE C282Y gene mutation could modify and drive the subgingival microbiota towards dysbiosis, which could participate in the periodontitis severity. The aim of this study was to investigate a putative association between the subgingival microbiota and serum iron biomarkers in GH patients from our previous study

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