The Role of Gut Microbiota in Osteoporosis Triggered by High-Fat Diets: Mechanisms and Targeted Therapeutic Strategies.

Overnutrition, and specifically a high-fat diet (HFD) in which more than 30% of energy intake is derived from fat, has been unequivocally identified as a modifiable risk factor for several major diseases including osteoporosis, cardiovascular disorders, diabetes, and metabolic syndrome. The continued rise in prevalence of osteoporosis, particularly among younger populations, along with widespread adoption of HFD, has made the underlying mechanisms and preventative strategies related to HFD-induced osteoporosis a primary focus in the field of bone metabolism research. Early studies suggested that HFD-mediated weight gain might confer protective effects on skeletal health. However, emerging evidence reveals that HFD disrupts bone metabolic homeostasis and accelerates the progression of osteoporosis through multiple pathways, including pathological expansion of adipose tissue, systemic chronic inflammation, and gut microbial dysbiosis. The gut microbiota (GM) is a crucial mediator of dietary fat absorption and is increasingly recognized as a pivotal factor in the pathogenesis of HFD-associated osteoporosis. HFD-induced alterations in gut microbial composition and metabolic function compromise intestinal barrier integrity, triggering chronic systemic inflammation and metabolic disturbances that collectively exacerbate bone loss and promote osteoporosis. Targeted microbiota interventions have shown promise in ameliorating bone deterioration, paving the way for innovative therapeutic approaches against HFD-related osteoporosis. This review systematically examines the pathways through which HFD induces osteoporosis via modulation of GM, and evaluates emerging microbiota-focused treatment strategies.