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, 8 (1), 15532

Increased Transferrin Saturation Is Associated With Subgingival Microbiota Dysbiosis and Severe Periodontitis in Genetic Haemochromatosis

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Increased Transferrin Saturation Is Associated With Subgingival Microbiota Dysbiosis and Severe Periodontitis in Genetic Haemochromatosis

Emile Boyer et al. Sci Rep.

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Alpha diversity analysis of subgingival microbiota samples. (A) Rarefaction curves. The data are presented as the mean ± standard deviation. (B) Richness index Sobs. The data are presented as the mean ± standard error. (C) Shannon-Weaver evenness index. The data are presented as the mean ± standard error. The results are presented according to the study groups: normal transferrin saturation (TSAT) (≤45%; n=21) and high TSAT (>45%; n=45). Alpha diversity metrics were calculated after subsampling to obtain equal numbers of sequences per library. Mann-Whitney and Student’s t test returned no significant differences in alpha diversity measures between the normal and high TSAT samples (p>0.05).
Figure 2
Figure 2
Beta diversity analysis illustrating the community structure of the subgingival microbiota. (A,B) Different views of the 3D PCoA plots calculated with Bray-Curtis metrics. (C,D) Different views of the 3D PCoA plots calculated with weighted UniFrac metrics. Green, TSAT ≤ 45%; red, TSAT > 45%.
Figure 3
Figure 3
Analysis of taxa relative abundances according to the TSAT level. Taxa showing significant differences in the LEfSe analysis. The percentages are the average relative abundances of the corresponding taxa in the related TSAT group.
Figure 4
Figure 4
Bacterial co-occurrence patterns with serum iron biomarkers according to the TSAT level. (A) Co-occurrence patterns of genera present in at least 70% of patients with normal TSAT (n=21); a total of 37 bacterial nodes, TSAT, ferritin and 144 edges are represented. (B) Co-occurrence patterns of genera present in at least 70% of patients with high TSAT (n=45); a total of 34 bacterial nodes, TSAT and 64 edges are represented. The edges represent 1 (thin line) or 2 or 3 (thick line) significant co-occurrence tests between nodes (green, positive; red, negative). The bacterial node colours represent the number of partners ranging from 1 (light green) to 11 (red); the serum iron biomarkers are shown in blue. The bacterial node sizes represent the mean relative abundance of each taxon.
Figure 5
Figure 5
Correlations between microbiota and clinical parameters in patients with normal TSAT (≤45%). (A) Correlation matrix among genera found in the co-occurrence network of patients with normal TSAT, serum iron biomarkers and periodontitis measures computed with Spearman’s test. Genera from the co-occurrence network that had an average relative abundance ≥0.5% were used to generate the correlation matrix. Green squares indicate clusters identified in the co-occurrence network. Black squares indicate significant Spearman’s correlations between genera and clinical parameters (p<0.05). The average relative abundances of genera are presented in the bar chart on the left side of the matrix. Spearman’s coefficient values are depicted using the colour gradient scale. (BD) Scatterplots of significant correlations between species level taxa and TSAT. Blue lines plot the linear regression slopes.
Figure 6
Figure 6
Correlations between microbiota and clinical parameters in patients with high TSAT (>45%). (A) Correlation matrix among genera found in the co-occurrence network of patients with high TSAT, serum iron biomarkers and periodontitis measures computed with Spearman’s test. Genera from the co-occurrence network that had an average relative abundance ≥0.5% were used to generate the correlation matrix. Green squares indicate clusters identified in the co-occurrence network. Black squares indicate significant Spearman’s correlations between genera and clinical parameters (p<0.05). The average relative abundances of genera are presented in the bar chart on the left side of the matrix. Spearman’s coefficient values are depicted using the colour gradient scale. (BG) Scatterplots of significant correlations between species level taxa and periodontitis measures. Blue lines plot the linear regression slopes.

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