肠道菌群及其代谢物与骨代谢的关系及其潜在机制的研究进展

随着人口老龄化的发展,骨质疏松的发病率越来越高,其并发的骨折也给社会和家庭带来沉重的经济负担。近年来许多研究表明肠道菌群可影响机体骨代谢,其中涉及的可能机制大部分尚未明确。肠道菌群定植在人体肠道中,可通过发酵产生大量的代谢产物如短链脂肪酸（short chain fatty acids,SCFAs）、吲哚衍生物、多聚胺、腺苷三磷酸（adenosine triphosphate,ATP） 等,可能对骨代谢产生重要的影响。其中以短链脂肪酸的研究最多,短链脂肪酸可促进骨形成,其影响骨代谢的机制可能是通过促进胰岛素样生长因子1（insulin-like growth factor-1,IGF-1）、胰高血糖素样肽1（glucagon-like peptide-1,GLP-1）的分泌而间接起作用。此外,植物雌激素、膳食植物多酚对骨代谢具有保护作用,这些作用依赖肠道菌群的存在。肠道菌群可将植物雌激素、膳食植物多酚等分解为具有更大活性的代谢物,从而对骨代谢产生调控作用。本文通过对肠道菌群及其代谢物与骨质疏松的相关性研究进行综述,总结了肠道菌群代谢物的种类、与骨代谢的关系以及其调控骨代谢的潜在机制,为肠道菌群防治骨质疏松的进一步机制研究奠定基础。     

脂肪棕色化调节骨代谢的研究进展

骨代谢包括骨形成和骨吸收两个过程, 两者维持体内骨代谢稳态。脂肪棕色化是将体内储存能量的白色脂肪转化为产热的棕色脂肪的生物学过程, 受环境、运动、营养素及信号分子诱导。脂肪棕色化能调节体内骨代谢, 通过分泌脂肪因子, 如成纤维生长因子-21、脂联素、胰岛素样生长因子-1、骨形态发生蛋白等影响成骨、破骨能力。脂肪棕色化也可通过肠道微生物群介导, 经免疫途径影响骨代谢。衰老机体脂肪棕色化能力降低, 与骨质疏松状态下骨代谢失调有关;而儿童和青少年脂肪棕色化活跃, 骨代谢维持健康状态。通过运动、补充营养素(辣椒素、白藜芦醇、槲皮素等)等方式可促进脂肪棕色化并维持棕色脂肪组织, 对机体骨代谢起到积极作用。未来, 明确脂肪棕色化与骨代谢之间具体的调节模式, 对干预脂肪棕色化治疗骨代谢相关疾病具有重要意义。     

基于肠-骨轴探讨肠道菌群对骨代谢影响的研究进展

肠道菌群被称为人体第二大基因库,在骨稳态中发挥着极其重要的作用,这也被越来越多的研究所证实。虽然骨重建的自然生理过程与骨吸收的发病机制已经比较清楚,但肠道菌群与骨代谢的关系仍未完全明确。肠-骨轴一词可被用来概括肠道微生物调控骨代谢的途径。根据现有研究,肠道菌群调节骨代谢的机制主要从菌群及营养物质代谢产物、免疫调节、肠粘膜屏障、内分泌调节等几个方面进行论述。笔者旨在通过总结肠道菌群对骨代谢影响的研究进展,为基于肠道菌群治疗部分骨科疾病提供理论参考。     

益生菌/益生元调节骨代谢机制的研究进展

近年来,肠道微生物影响宿主骨代谢得到了深入研究,特别是益生菌/益生元通过调节肠道微生物防治代谢性骨病的研究取得了长足的进步。本文基于相关文献,从调节免疫功能、调节肠上皮屏障功能、调节短链脂肪酸代谢等方面,对益生菌/益生元影响骨代谢、防止骨量丢失的机制进行综述,以期为代谢性骨病的防治提供新思路、新方法。     

肠道菌群骨代谢动物模型建立与干预的研究

肠道微生物群（gut microbiota,GM）或其代谢产物对骨骼发育的作用被称为肠-骨轴（Gut-bone axis）。目前已有多项研究对肠-骨轴的作用机制和途径进行阐述,但由不同的动物模型或干预策略所得出的结果有显著差异。因此,选择合适的动物模型和干预策略是研究GM对骨骼发育影响的关键。该文对有关肠-骨轴研究的动物模型选择、干预策略、结果评估和潜在治疗靶点进行系统综述,旨在帮助研究人员更加准确地选择合适的动物模型和干预策略。     

细胞因子与骨质疏松症

骨质疏松症是老龄化社会常见的复杂性疾病,发病机制主要为骨代谢平衡障碍,骨吸收大于骨形成。近年研究发现,体内骨形态发生蛋白（BMP）、胰岛素样生长因子（IGF）、转化生长因子-α（TGF-α）、成纤维生长因子（FGF）等也参与骨质疏松发生过程的调控,与传统的雌激素、甲状腺素等相比,可能起着更为关键的作用,即通过直接或间接的形式调节骨细胞有丝分裂,并促进骨细胞分化和骨形成等。该文就这些细胞因子与骨质疏松的关系作一综述。     

胆固醇对骨代谢影响的研究进展

正常骨代谢是动态调节的周期过程,破骨细胞负责的骨吸收与成骨细胞负责的骨形成相互偶联维持动态平衡。当骨形成和骨吸收的动态平衡被破坏时,就会引起骨量丢失及相关骨病。流行病学证据表明,胆固醇会抑制或促进骨代谢,这取决于胆固醇的种类。胆固醇及其代谢产物通过调节成骨细胞和破骨细胞的分化及活化来影响骨代谢的动态平衡。本文就胆固醇对骨代谢影响的研究进展作一综述。     

中药通过调控短链脂肪酸防治骨质疏松症的研究进展

肠道菌群微生物是与宿主共生的一个大的生物群落，当其发生紊乱时将会导致多种疾病的发生，尤其是全身代谢性疾病。其代谢产物也对全身代谢性疾病起到重要的调控作用，尤其是骨代谢性疾病。短链脂肪酸(short chain fatty acids, SCFAs)是肠道微生物群所产生的一类代谢产物，能够很好地反映肠道菌群微生物的功能，大量的研究证明其在骨代谢性疾病中起着调控作用。中药在调控肠道菌群微生物及其代谢产物中有很大的作用，尤其是对于SCFAs的调控。笔者就单味中药及提取物与中药复方通过调控SCFAs影响骨代谢，从而在防治骨质疏松症方面的研究进行总结，以期为骨质疏松症的预防和治疗提供新思路。     

肠道菌群对骨代谢影响的研究进展

肠道菌群在人体中发挥着重要的作用,与人体的骨量减低及骨质疏松的发病相关。其可能通过自身代谢产物,影响宿主代谢及免疫系统等几方面来影响破骨细胞和成骨细胞的相对活性,从而影响骨代谢,甚至导致骨质疏松。本文将从上述几个方面对肠道菌群对骨代谢的影响进行综述。     

PTH对骨髓细胞骨代谢相关基因表达的影响

目的观察大鼠骨髓微环境骨代谢相关基因表达变化,拟探讨外源性甲状旁腺激素（Parathyroidhormone PTH）治疗骨质疏松的分子机制.方法给予卵巢摘除（ovariectomy OVX）诱导的骨质疏松（Osteoporosis OP）大鼠每天20 μg/kg重组人甲状旁腺激素[rhPTH（1-34）]治疗8周,采用RT-PCR方法检测大鼠骨髓细胞骨代谢相关基因的表达,比较PTH用药前、后及停药后各基因表达的变化.结果显示用药后骨髓细胞中成骨活性基因ALP、BGP、Cbf α1表达均持续显著升高（P＜0.05～0.001）;破骨细胞调节基因M-CSF与RANKL表达变化无统计学意义;OPG与TRAF-6表达呈双相波动（P＜0.05～0.01）;RANKL/OPG比值在用药1周时增加（P＜0.05）;IL-6表达呈早期短时升高（P＜0.01）.结论PTH对骨质疏松的治疗作用可能与其持续增强骨髓细胞的成骨活性基因表达,调节破骨细胞分化和功能成熟基因表达有关.     

肠菌移植治疗骨质疏松症的研究进展及临床前景

骨质疏松症是临床上常见的骨代谢性疾病,骨折风险高,致残、致死率高.我国正逐步进入老龄化社会,骨质疏松症已经成为影响老年人身体健康的重大公共健康问题.近年来,肠道菌群与骨代谢的关联受到了越来越多的关注,肠道菌群与骨质疏松症之间存在密切关系.肠菌移植是指将肠道菌群从健康的供体转移到肠道菌群失调的受体,其目的是恢复肠道微生物...     

短链脂肪酸通过免疫机制和内分泌环境影响骨代谢的机制进展

肠道菌群对维持人体健康起重要作用。短链脂肪酸(short-chain fatty acid, SCFAs)是肠道微生物群分解膳食纤维所形成的主要代谢产物,可以影响成骨细胞和破骨细胞的增殖和分化。近年来研究发现,SCFAs不仅可以通过影响免疫细胞,例如T细胞、B细胞调控骨代谢,还可以通过影响激素,例如胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)的分泌来发挥调控骨代谢的作用。笔者介绍了SCFAs通过免疫机制、内分泌环境影响骨代谢的作用机制,为骨质疏松的机制研究提供新的思路。     

从骨免疫学到骨微生物学：肠道微生物如何调节骨骼

肠道微生物群被称为人体的第二个基因库,在维持人体平衡中起主要作用。不良饮食习惯、抗生素滥用、病理状态和生活环境改变会对肠道菌群产生负面影响,以引起多种疾病。最新研究发现肠道微生物群与骨质疏松症之间有着密切的联系,同时引入了一个新术语"骨微生物学",该研究领域旨在弥合骨骼生理学、胃肠病学、免疫学和微生物学之间的差距。本文简要介绍了肠道菌群通过免疫系统、新陈代谢和内分泌环境以及其他因素影响骨代谢的潜在机制,通过研究肠道菌群与骨骼健康之间的关系,不仅对于维持骨骼健康和最大程度地减少骨质疏松症很重要,而且对于肠道微生物群是否可作为骨质疏松症新型治疗靶标以及是否可用作骨折预测的生物标志物方面具有重要意义。     

Bone Health in Women With Polycystic Ovary Syndrome: A Narrative Review

Bone as an active connective and endocrine tissue is influenced by hormones, physical activity, inflammatory factors, minerals, dietary components, and body weight. Bone fractures are a major cause of decreased quality of life and mortality in humans. Polycystic ovary syndrome (PCOS), is one of the most common endocrine disorders in women of reproductive age worldwide. PCOS is associated with disturbances in androgen and estrogen levels, insulin resistance (IR), obesity, as well as low-grade chronic inflammation, and gut microbiota (GM) dysbiosis, all of which may negatively or positively affect bone metabolism. However, it has not yet been well clarified whether PCOS is bone-protective or bone-destructive. This study aimed to review the association between bone health and PCOS, and summarize its related factors. PubMed, Scopus, and Web of Science databases were searched to retrieve relevant English publications investigating the relationship between bone health and PCOS. Several disorders associated with PCOS can negatively or positively affect bone metabolism. Despite some positive effects of insulin, androgens, estrogens, and obesity on bone, IR, estrogen deficiency, low-grade chronic inflammation, and GM dysbiosis may adversely affect the bone metabolism in PCOS women. Studies comparing bone mineral density or bone metabolism and the risk of bone fractures in women with PCOS have controversial results. Further studies are required to understand the mechanisms underlying bone metabolism in PCOS subjects. Moreover, prospective studies are needed to estimate the risk of bone fractures and osteoporosis in PCOS subjects.     

Intermittent Parathyroid Hormone Alters Gut Microbiota in Ovariectomized Osteoporotic Rats

ObjectiveTo investigate the effect of intermittent parathyroid hormone (PTH) on gut microbiota (GM) in ovariectomized (OVX) osteoporotic rats.MethodsThirty female Sprague–Dawley rats were divided into three groups: sham‐operation (SHAM) group, OVX group and PTH treatment group. After 3 months of treatment, the femurs, serum and feces were acquired for micro‐CT, biochemical analysis and 16S rRNA sequencing, respectively. For 16S rRNA sequencing, after raw reads filtrated and chimera sequences removed, the clean reads were obtained. According to these clean reads, the operational taxonomic units (OTUs) were clustered. Venn diagram analysis was conducted to explore common and unique GM among the three groups. The α‐diversity analysis including Shannon and Simpson indexes were used to evaluate the richness and diversity of the GM. The β‐diversity analysis was performed to estimate the structure of GM. The metabolic function was predicted by Tax4Fun analysis.ResultsWith micro‐CT and biochemical analysis, significant improvements were found in the PTH group compared with the OVX group. In Venn diagram analysis, more unique OTUs were found in the SHAM and PTH groups than the OVX group. According to the rank abundance curve, the SHAM and PTH groups had similar richness and evenness, which were higher than the OVX group. Simpson and Shannon indexes were higher in the SHAM and PTH groups compared with the OVX group, indicating that the SHAM and PTH groups had higher microbiota complexity than the OVX group. In β‐diversity analysis, apparent separation was found in the OVX group from the PTH and SHAM groups, which suggested that osteoporosis is the critical factor influencing the GM composition and PTH treatment and can restore the structure of GM. Compared with the OVX group, treatment with PTH increased the abundances of GM which were reported to increase bone mass, such as Lactobacillus_reuteri, Muribaculaceae, Ruminococcaceae, and Clostridia, and inhibited the relative abundance of Rikenellaceae, which was reported to be potentially related to osteoporosis. GM function analysis showed that PTH could promote butyrate synthesis. In Tax4Fun analysis, the function of butanoate metabolism is more vital in the PTH group than the OVX and SHAM groups, suggesting PTH treatment could regulate microbial metabolic function, including butanoate metabolism.ConclusionIntermittent PTH can interact with GM through increasing the abundance of probiotics and reducing the abundance of the pathogenic bacteria to enhance the bone mass.     

肠道菌群调节肠道MicroRNA治疗骨质疏松症

骨质疏松症是以骨量减少,骨组织结构退化进而极易导致骨质疏松性骨折的一类疾病。严重影响患者生活质量,同时也带来了极大的经济负担。近年来有关调节肠道菌群进而干预骨质疏松症的研究逐渐兴起。炎症性肠病是由肠道菌群失调引起的炎症免疫变态反应,而炎症性肠病与骨量丢失密切相关。近来有研究表明肠道菌群与肠道MicroRNA直接的相互作用可以治疗炎症性肠病。为此,我们提出设想,肠道菌群可能调节肠道MicroRNA具有治疗骨质疏松症潜力,现从肠道菌群与骨质疏松症;MicroRNA与骨质疏松症;肠道菌群与MicroRNA;炎症性肠病与骨质疏松症四方面展开综述,支持肠道菌群通过调节肠道MicroRNA治疗骨质疏松症的观点,为骨质疏松症治疗提供新思路。