Increased transferrin saturation is associated with subgingival microbiota dysbiosis and severe periodontitis in genetic haemochromatosis

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.

Iron overload and periodontal status in patients with sickle cell anaemia: A case series

“…Conversely, serum ferritin level was not associated with any of the outcomes of this study, which corroborates the results reported in previous studies (Boyer et al, 2018; Meuric et al, 2017). Evaluation of serum transferrin saturation and ferritin levels is the least expensive and most widely available method for investigating iron overload.…”

“…These results suggest that patients with SCA and high serum transferrin saturation level are at a higher risk of developing more severe periodontal disease. From this viewpoint, our results corroborate those reported in studies on patients with haemochromatosis (Boyer et al, 2018; Meuric et al, 2017), among which serum transferrin saturation levels of >45% were associated with severe periodontitis. These findings suggest common mechanisms underlying the association between iron overload and periodontitis severity in both conditions (SCA and haemochromatosis).…”

“…In vivo studies have demonstrated that periodontopathogens, such as P . gingivalis , can cleave the transferrin detected in gingival crevicular fluid to produce iron and peptides that favour the growth of asaccharolytic bacteria present in the periodontal pocket (Boyer et al, 2018; Duchesne, Grenier, & Mayrand, 1999; Goulet et al, 2004; Inoshita, Iwakura, Amano, Tamagawa, & Shizukuishi, 1991). When the binding capacity of transferrin to iron is saturated (>45%), nontransferrin‐bound iron becomes detectable in plasma and free iron begins to deposit on tissues.…”

“…Another possible explanation for our findings is that iron‐containing transferrin fragments or iron release may promote the production of cytotoxic hydroxyl radicals, which results in the degradation of periodontal tissues (Goulet et al, 2004). Thus, increases in serum transferrin saturation levels with consequent increases in iron bioavailability may promote dysbiosis of periodontal microbiota (Boyer et al, 2018) and regulate host immunoinflammation, thereby contributing to a greater extent of periodontitis.…”

Periodontal pathogens and clinical parameters in chronic periodontitis

“…We have worked on a cohort of patients with chronic periodontitis and hemochromatosis that allowed us to show worsened periodontal measures in case of iron overload (Meuric, Lainé, et al, ). An early study (with 66 patients) of their subgingival microbiota showed a potential impact of iron through correlations between transferrin saturation and the abundance of Porphyromonas and Treponema (Boyer et al, ). Nevertheless, an extensive characterization of their microbiota (including dysbiosis) has not been performed yet, regarding occurrence and abundance of well‐known and newly identified potential periodontal pathogens, as well as their relationship with periodontal measures.…”