Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Pineal Research Pub Date : 2024-04-15 DOI:10.1111/jpi.12954
Yueqi Chen, Chuan Yang, Zihan Deng, Tingwen Xiang, Qingrong Ni, Jianzhong Xu, Dong Sun, Fei Luo
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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.

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肠道微生物产生的色氨酸代谢物褪黑激素通过调节 SCFA 和 TMAO 代谢改善骨质疏松症
骨质疏松症(OP)是一个严重的全球性健康问题,对生产力和人类寿命有重大影响。肠道微生物群失调已被证实与骨质疏松症的进展密切相关。褪黑素(MLT)是一种重要的内源性激素,可调节骨代谢、维持骨平衡并改善骨质疏松症的进展。多项研究表明,褪黑激素参与调节肠道微生物群和肠道屏障功能。然而,肠道微生物群衍生的 MLT 对 OP 的积极影响仍不清楚。在这里,我们发现 OP 会导致肠道色氨酸紊乱并减少肠道微生物群衍生的 MLT 的产生,而服用 MLT 可减轻 OP 相关的临床症状并逆转肠道微生物群失调,包括肠道微生物群的多样性、许多益生菌(如 Allobaculum 和 Parasutterella)的相对丰度以及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 能明显增加短链脂肪酸的产生,减少三甲胺 N-氧化物相关代谢物的产生。重要的是,MLT 可以调节 M1/M2 巨噬细胞的动态平衡,降低血清中促炎细胞因子的水平,并恢复肠道屏障功能。综上所述,我们的研究结果强调了肠道微生物衍生的 MLT 通过与 SCFA 代谢相关的 "肠-骨 "轴在 OP 进展中的重要作用,这可能为开发 MLT 作为治疗 OP 的药物提供了新的见解。
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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
期刊最新文献
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