Potential roles of gut microbiota in metal mixture and bone mineral density and osteoporosis risk association: an epidemiologic study in Wuhan

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/cm 2 , 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.