Abstract
Few studies have focused on the effects of multiple metal mixtures on bone health and the underlying mechanisms related to alterations in the gut microbiota. This study aimed to examine the potential roles of gut microbiota alterations in metal mixtures and their association with osteoporosis traits. Adults aged ≥ 55 years were recruited from two community healthcare centers in Wuhan City during 2016–2019. The plasma concentrations of six metals (zinc, iron, selenium, lead, cadmium, and arsenic) were measured using an inductively coupled plasma mass spectrometer. The k-means clustering method was employed to explore the exposure profiles of metal mixtures for all participants. 16S rRNA gene sequencing was used to profile the gut microbiota of participants. Combining these results with those of our previous study, we identified overlapping taxa and evaluated their potential roles. A total of 806 participants (516 females), with an average age of 67.36 years were included. The participants were grouped into three clusters using k-means clustering: Cluster 1 (n = 458), Cluster 2 (n = 199), and Cluster 3 (n = 149). The high-exposure group for iron, zinc, lead, and cadmium (Cluster 3) showed a negative association with lumbar spine 1–4 bone mineral density (BMD). A total of 201 individuals (121 females) underwent sequencing of the gut microbiota. Both alpha and beta diversities were statistically different among the three groups. Bacteroidaceae, Lachnospiraceae, Bifidobacteriaceae, Bacteroides, and Lachnospiraceae_incertae_sedis were identified as overlapping taxa associated with the metal mixtures and BMD. Interaction analysis revealed that Cluster 3 interacted with Bacteroidaceae/Bacteroides, resulting in a positive effect on LS1-4 BMD (β = 0.358 g/cm2, 95% CI: 0.047 to 0.669, P = 0.025). Our findings indicate associations between multiple metal mixtures and BMD as well as gut microbiota alterations. Exploring the interaction between metal mixtures and the gut microbiota provides new perspectives for the precise prevention and treatment of osteoporosis.
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Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The data are not publicly available due to privacy or ethical restrictions.
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Acknowledgements
We thank all participants for their contributions to this work. We would also like to thank the Wuhan Center for Disease Control and Prevention for their technology assistance.
Funding
This work was supported by the National Natural Science Foundation of China (Grant no.82273711) and Wuhan Municipal Health Commission (Grant no.WY22B06).
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Jianli Zhang: Develop the research plan, detection of metals in plasma samples, application statistical techniques to analyze study data, write the initial draft and revision. Qi Mai: Detection of metals in plasma samples, write the initial draft and revision. Dongsheng Di, Haolong Zhou, Ruyi Zhang: Data collection, development of the methodology and participant in the article revision. Qi Wang: Coming up with ideas, obtaining financial support for the project that led to this publication, supervision, project management, and writing-review and editing.
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This study was approved by the Ethics Committee of Tongji Medical College of Huazhong University of Science and Technology. Each participant had signed an informed consent form.
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Jianli Zhang and Qi Mai contributed equally to this work.
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11356_2023_30388_MOESM1_ESM.tif
Fig. S1 Heatmap illustration of pairwise correlations in plasma concentrations of Fe, Zn, Se, As, Cd, and Pb. Red × indicated there was no significant correlation between the two metals (TIF 40495 KB)
11356_2023_30388_MOESM2_ESM.tif
Fig. S2 Violin plot of the six metals in plasma (Fe, Zn, Se, As, Cd, and Pb) grouped by the three clusters observed by k-means clustering method among 806 participants. Cluster 1, low-exposure group for all six metals; Cluster 2, high-exposure group for Se and As; Cluster 3, high-exposure group for Fe, Zn, Pb, and Cd (TIF 44488 KB)
11356_2023_30388_MOESM3_ESM.tif
Fig. S3 Bacterial community abundance barplot of each group: (A) Bacterial community abundance barplot at phylum level, (B) Bacterial community abundance barplot at family level. Cluster 1, low-exposure group for all six metals; Cluster 2, high-exposure group for Se and As; Cluster 3, high-exposure group for Fe, Zn, Pb, and Cd (TIF 13365 KB)
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Zhang, J., Mai, Q., Di, D. et al. Potential roles of gut microbiota in metal mixture and bone mineral density and osteoporosis risk association: an epidemiologic study in Wuhan. Environ Sci Pollut Res 30, 117201–117213 (2023). https://doi.org/10.1007/s11356-023-30388-w
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DOI: https://doi.org/10.1007/s11356-023-30388-w