Gut microbiota mediated the curvilinear association between dietary animal protein intake and bone mineral density in Chinese adults

Dietary protein intake is closely related to bone health. However, it remains unclear how different dietary protein sources contribute to bone mass and how the gut microbiota affects these processes. This study investigated the relationships of dietary animal and plant protein intake with bone mineral density (BMD) and the mediating role of gut microbes in these associations. A total of 1012 participants aged 18-64 years were recruited. Dietary protein intake was assessed using a food frequency questionnaire. BMD was measured by dual-energy X-ray absorptiometry. The gut microbiota was analysed by 16S rRNA sequencing. The relationships between dietary protein intake and BMD and the mediating effects of gut microbes were examined. Dietary animal protein intake showed inverted U-shaped relationships with BMD at the lumbar spine, total hip and whole body (<i>P</i> < 0.050). A positive association was observed between them in the subpopulation with an intake level below 0.87 g kg^-1 day^-1 (sβ = 0.095 to 0.107, <i>P</i> < 0.050). Among individuals with intake levels higher than this threshold, a linear downward trend was observed (<i>P</i> < 0.050). Dietary plant protein intake was inversely associated with BMD at the lumbar spine (sβ = -0.192, <i>P</i> = 0.002) and total hip (sβ = -0.173, <i>P</i> = 0.008). Eleven and two bacterial genera were associated with dietary animal and plant protein intake, respectively (<i>q</i>-value < 0.250). <i>Lactococcus</i>, <i>Lactonifactor</i>, <i>Lachnoclostridium</i>, <i>Coprococcus_1</i> and <i>Dialister</i> together mediated 14.50%-18.66% of the associations between dietary animal protein intake and BMD at the three skeletal sites. In conclusion, the threshold effect of dietary animal protein intake on BMD was partly explained by some gut microbes. Excessive dietary animal protein intake and general dietary plant protein intake might not have positive effects. These findings may provide important insights into the prevention and management of osteoporosis.