High-fat diet, intestinal microecology and bone loss.

Bone, a vital component of the human body, plays a crucial role in maintaining mobility and systemic health. Growing evidence underscores the complex interplay between a high-fat diet (HFD), intestinal microecology, and bone loss. This review consolidates findings across three interconnected mechanisms: (1) HFD compromises bone homeostasis by reducing bone mineral density (BMD) and disrupting microarchitecture, driven by bone marrow adiposity, oxidative stress, and chronic inflammation; (2) HFD disrupts intestinal microecology through microbiota dysbiosis (e.g., elevated Firmicutes/Bacteroidetes ratio, depletion of Bifidobacterium), epithelial barrier impairment (e.g., suppressed Mucin2 secretion, downregulated tight junction proteins), and immune dysregulation (e.g., Th17/Treg imbalance, diminished IL-10 production); and (3) intestinal microecology imbalances exacerbate bone loss through microbial metabolite alterations (e.g., a deficiency of short-chain fatty acids impairing Treg-mediated Wnt10b signaling), systemic inflammation from barrier leakage, and intestinal immune cell trafficking (e.g., Th17 migration to bone marrow). These interconnected mechanisms point to an indirect pathway by which HFD contributes to bone loss through alterations in intestinal microecology. While this indirect relationship remains insufficiently validated, accumulating evidence highlights the important roles of HFD and intestinal microecology in bone regulation. This review aims to comprehensively examine the connections between HFD, intestinal microecology, and bone loss, with a focus on elucidating these potential mechanisms. Given diet's profound impact on intestinal microecology, optimizing dietary patterns to rebalance intestinal microecology offers a promising strategy for preventing and treating bone-related disorders.