关键词: gut microbiota osteoporosis postmenopausal women serum metabolites tryptophan-indole metabolism

Mesh : Humans Gastrointestinal Microbiome Female Bone Density Postmenopause / blood Feces / microbiology Middle Aged RNA, Ribosomal, 16S / genetics Metabolomics Bacteria / classification genetics metabolism Aged Metabolome Biomarkers / blood Chromatography, Liquid Mass Spectrometry Osteoporosis, Postmenopausal / blood microbiology Bone Remodeling

来  源:   DOI:10.3389/fcimb.2024.1367325   PDF(Pubmed)

Abstract:
UNASSIGNED: Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women.
UNASSIGNED: In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis.
UNASSIGNED: The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene.
UNASSIGNED: Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis.
摘要:
新的证据表明,肠道微生物群与骨骼稳态密切相关。然而,关于骨密度(BMD)指数之间的关系知之甚少,骨转换标记,以及绝经后妇女的肠道菌群及其代谢产物。
在这项研究中,了解绝经后BMD降低妇女的肠道微生物群特征和血清代谢物变化,我们招募绝经后BMD正常或降低的个体,并将其分为正常组和OS组.收集粪便和血清样品进行16SrRNA基因测序,基于液相色谱与质谱联用(LC-MS)的代谢组学和综合分析。
结果表明,OS组的细菌丰富度和多样性大于正常组。此外,在两组中发现了区别细菌,并与BMD指数和骨转换标志物密切相关。代谢组学分析显示,血清代谢物的表达,例如etiocholanolone,硫酸睾酮,和吲哚-3-丙酮酸,以及相应的信号通路,尤其是那些参与色氨酸代谢的人,脂肪酸降解和类固醇激素的生物合成,也发生了重大变化。相关分析显示,富含正常组的拟杆菌丰度与富含正常组的etocholanone和硫酸睾酮丰度呈正相关;特别是,拟杆菌与BMD呈正相关。重要的是,色氨酸-吲哚代谢途径由肠道细菌来源的tnaA基因独特地代谢,正常组的预测丰度明显高于对照组,拟杆菌的丰度与tnaA基因密切相关。
我们的结果表明,绝经后妇女的肠道微生物群和血清代谢物存在明显差异。特定改变的细菌和衍生的代谢物与BMD指数和骨转换标志物密切相关,表明肠道微生物群和血清代谢物作为预防骨质疏松症的可改变因子和治疗靶点的潜力。
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