Abstract：
Osteoporosis (OP) is a severe global health issue that has significant implications for productivity and human lifespan. Gut microbiota dysbiosis has been demonstrated to be closely associated with OP progression. Melatonin (MLT) is an important endogenous hormone that modulates bone metabolism, maintains bone homeostasis, and improves OP progression. Multiple studies indicated that MLT participates in the regulation of intestinal microbiota and gut barrier function. However, the promising effects of gut microbiota-derived MLT in OP remain unclear. Here, we found that OP resulted in intestinal tryptophan disorder and decreased the production of gut microbiota-derived MLT, while administration with MLT could mitigate OP-related clinical symptoms and reverse gut microbiota dysbiosis, including the diversity of intestinal microbiota, the relative abundance of many probiotics such as Allobaculum and Parasutterella, and metabolic function of intestinal flora such as amino acid metabolism, nucleotide metabolism, and energy metabolism. Notably, MLT significantly increased the production of short-chain fatty acids and decreased trimethylamine N-oxide-related metabolites. Importantly, MLT could modulate the dynamic balance of M1/M2 macrophages, reduce the serum levels of pro-inflammatory cytokines, and restore gut-barrier function. Taken together, our results highlighted the important roles of gut microbially derived MLT in OP progression via the \"gut-bone\" axis associated with SCFA metabolism, which may provide novel insight into the development of MLT as a promising drug for treating OP.
摘要：
骨质疏松症（OP）是一个严重的全球健康问题，对生产力和人类寿命具有重大影响。肠道菌群失调已被证明与OP进展密切相关。褪黑素(MLT)是调节骨代谢的重要内源性激素,维持骨骼稳态，并改善OP进展。多项研究表明，MLT参与肠道菌群和肠道屏障功能的调节。然而,肠道菌群来源的MLT在OP中的有希望的作用仍不清楚。这里,我们发现OP会导致肠道色氨酸紊乱，并减少肠道菌群来源的MLT的产生，虽然MLT的给药可以减轻OP相关的临床症状和逆转肠道菌群失调，包括肠道微生物群的多样性，许多益生菌的相对丰富，例如Allobaculum和Parasutterella，和肠道菌群的代谢功能，如氨基酸代谢，核苷酸代谢，和能量代谢。值得注意的是,MLT显着增加了短链脂肪酸的产生，并减少了三甲胺N-氧化物相关的代谢产物。重要的是,MLT可以调节M1/M2巨噬细胞的动态平衡，降低血清促炎细胞因子水平，并恢复肠道屏障功能。一起来看,我们的结果强调了肠道微生物来源的MLT通过与SCFA代谢相关的“肠-骨”轴在OP进展中的重要作用，这可能为MLT作为治疗OP的有希望的药物的开发提供新的见解。
