消化系统疾病并发骨质疏松症与肠道菌群的关系探讨

随着全球人口老龄化,骨质疏松症的发病率逐年增高,在我国,50岁以上人群中骨质疏松症总患病率达15.7%,预计到2020年,我国骨质疏松和低骨量患者将增加至2.8亿,骨质疏松症已经成为影响我国老年人口生活质量的重大公共卫生问题。消化系统疾病并发骨质疏松症,其发生机制较复杂,目前仍未彻底阐明,常常并发骨质疏松症的消化系统疾病有胃切除术后、慢性肝脏疾病、炎症性肠病等。研究发现,消化系统疾病伴随着肠道菌群的失调,而肠道菌群与骨质疏松症从发病、发展及治疗等方面关系密切,越来越多的研究表明肠道菌群失衡与多种代谢性疾病的发生发展紧密相关,因此,骨质疏松症作为一种全身性骨代谢疾病,其与肠道菌群失衡之间的关系近年来逐渐受到关注。从肠道菌群的视角探讨消化系统疾病并发骨质疏松症的机制,对于开拓该类合并症的防治思路具有启示意义。     

酪酸梭菌联合阿仑膦酸钠治疗炎症性肠病合并骨质疏松症效果分析

目的探讨酪酸梭菌联合阿仑膦酸钠治疗炎症性肠病合并骨质疏松症近期疗效及对骨代谢、炎性因子和肠道菌群的影响。方法将80例炎症性肠病合并骨质疏松症患者随机分为对照组和观察组。除基础治疗外,对照组给予阿仑膦酸钠、观察组给予联合酪酸梭菌二联活菌胶囊治疗,持续3个月。比较两组临床疗效、骨密度(bone mineral density,BMD)、骨代谢指标、炎性因子及肠道菌群水平。结果与对照组相比,观察组治疗总有效率升高(95.0%vs 77.5%),腰椎、股骨颈及Ward三角区BMD水平升高;骨碱性磷酸酶(BALP)、骨钙素水平升高,1型胶原交联羧基末端肽(CTX)水平降低; IL-6、IL-17等炎性因子水平降低,粪便中大肠杆菌含量降低,双歧杆菌、乳酸杆菌含量增加,差异均有统计学意义(P均0.05)。结论酪酸梭菌联合阿仑膦酸钠治疗炎症性肠病合并骨质疏松症近期疗效好,能够增加BMD,改善骨代谢指标,减轻机体炎性反应,而且还能够调节肠道菌群,适于临床上应用。     

“后天养先天”理论探讨肠道菌群在肌少-骨质疏松症中的作用

随着全球人口老龄化进程不断加快，肌少-骨质疏松症受到全社会关注。肠道菌群是人体肠道生态系统的重要组成部分，被称为“人体第二基因库”，在调节肌骨代谢方面具有重要作用；肌少-骨质疏松症是老年人常见的代谢性疾病，对老年人的生活质量有较大的影响，该病在中医理论体系中归属于“痿证”。本文基于“后天养先天”理论的内涵介绍了肠-肌轴、肠-骨轴理论，证明肠道菌群与肌肉、骨骼之间存在相关性，即“微生物-肠-肌骨”之间具有密切联系；强调肠道菌群是肌少-骨质疏松症共同存在的发病因素。同时，基于“后天养先天”理论阐述中医药在调节肠道菌群、防治肌少-骨质疏松症方面具有明显优势，并综述文献说明目前研究现状，提出肌骨共治具有可行性的观点。旨在为深度研究肠道菌群与肌肉、骨骼分子间的联系，发挥中医药治疗肌少-骨质疏松症提供思路。     

肠道菌群在骨质疏松症发病机制中的研究

骨质疏松症是一种慢性全身性代谢性骨病，由于骨吸收与骨形成的失衡造成骨量减少及骨密度的降低，与此同时骨组织微结构的破坏导致骨折风险升高，影响患者的生活质量甚至威胁生命安全。对于骨质疏松症的发病机制，目前认为与激素、内分泌、免疫、肠道菌群等因素有关。近年来微生物-肠-骨轴成为了骨代谢领域的研究热点。本文将从肠道粘膜屏障、骨免疫学、肠道菌群代谢产物等方面对肠道菌群在骨质疏松症中的发病机制进行综述。     

中医药调控肠道菌群治疗绝经后骨质疏松症的研究进展

随着社会人口老龄化程度不断加重,绝经后骨质疏松症发病率逐年上升,其发病机制复杂,目前仍未完全阐明,越来越多的研究表明,肠道菌群与绝经后骨质疏松症关系密切,以肠道菌群视角探讨中医药调控骨内环境稳态是一个全新的视角。中医药通过肠道菌群防治绝经后骨质疏松症有着巨大的研究潜力,不失为一条新的有效治疗途径。该文结合国内外相关研究,总结肠道菌群调控绝经后骨质疏松症的理论研究、临床研究和作用机制研究,阐述“肝肾-肠”“脾-肠”“肺合大肠”“心合小肠”理论指导下的临床应用,归纳复方、中药（单体）、中成药以及其他中医药疗法通过肠道菌群改善骨骼健康的相关研究,以拓宽防治思路,为临床上通过调控肠道菌群防治绝经后骨质疏松症提供参考。     

基于肠道菌群探讨中医实脾防治骨质疏松症的机制

骨质疏松的发病机制较为复杂,研究发现肠道菌群与骨代谢关系密切,影响着骨质疏松症的发病及预后。中医学认为,骨质疏松症是脾肾亏虚所致。脾为气血生化、生痰之源,脾肾先后天相互资生。脾之功能与肠道菌群的作用极为相似,两者均能资先天脏腑,益骨生髓。近年来,随着中医学的不断创新和发展,实脾类药物调节肠道菌群防治骨质疏松症的相关研究成为热点。总结肠道菌群对骨代谢的影响及实脾类药物对肠道菌群的影响,以期为中医学从脾论治骨质疏松症提供科学依据,为中医药防治骨质疏松症提供新思路。     

肠道微生态失衡为骨质疏松症发病的易感因素

本文通过综述人体肠道菌群和骨代谢的相关性研究,从衰老与胃肠道功能不足是老年性骨质疏松的危险因素、炎症性肠病是并发骨质疏松的危险因素、糖皮质激素是IBD诱发骨质疏松的重要因素、肠道菌群失调是绝经后骨质疏松发生的关键因素等方面探讨了肠道微生态失衡与骨质疏松发生发展的相关性,并从肠道微生态出发对老年性骨质疏松的危险因素和绝经后骨质疏松发生的关键因素做了深入探讨,通过综述国内外实验和临床研究,认为肠道微生态失衡是骨质疏松症发病的易感因素。     

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。     

肠道免疫功能与骨代谢的研究进展

肠道黏膜屏障有助于防止肠道内菌群紊乱,食物、化学药物等直接与黏膜裸露面接触,这对于疾病的发生尤为重要,其免疫功能对机体的健康作用越来越受到人们的重视。肠道免疫功能具有一般性的屏障作用,还能参与体液免疫和细胞免疫过程,在机体肠道内环境的调节中起重要作用。肠道免疫屏障构成复杂且受肠道菌群、饮食等的影响,能通过多种途径影响骨代谢,与骨质疏松症的发生关系密切,研究肠道菌群、免疫系统、骨代谢三者的关系,有助于进一步阐明肠道菌群通过调控宿主免疫系统来作用于机体骨代谢的机制,这可能对临床治疗骨质疏松症提供一种新的思维策略。本文将从几个方面阐述肠道免疫功能与骨代谢的研究进展。     

肠道微生物与骨病的研究进展

人体肠道微生物菌群基因数量超过人体基因数量的100倍,被称为"人体第二基因库",这些基因赋予各种细菌不同的功能,产生极其复杂多样的代谢产物,对于调节人体消化、免疫、内分泌、乃至神经系统等功能具有重要作用。而处于稳态的肠道微生物不但能依附于肠黏膜表面形成保护屏障,阻止致病菌的生长、繁殖和入侵,还能通过黏膜系统促进免疫系统成熟,有助于机体有效抵抗病原微生物的感染。如果肠道菌群平衡被打破,那么宿主患各种疾病的风险就会随之升高。宿主健康与否会导致肠道微生物发生变化,进而通过间接刺激或抑制成骨细胞和激活破骨细胞而打破骨矿化平衡,影响骨健康。除此之外,它们还可以通过维持免疫系统稳态参与调控骨代谢,通过影响生长因子调节、营养物质吸收和宿主代谢通路等参与骨质疏松症、类风湿性关节炎和强直性脊柱炎等相关骨病的发生。目前关于肠道微生物菌群与骨病的研究较少,且多集中于菌群差异性对骨病的影响,而肠道菌群影响骨病的分子机制亟待进一步研究。本文就近年来国内外对肠道微生物与骨病关系的研究进展进行综述。     

Bone Health in Patients With Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD) is a chronic inflammatory medical condition with relapses and remission. Metabolic bone disease, including osteoporosis, is associated with IBD and imparts a significant morbidity if pathologic fractures were to occur. There has been a significant amount of research that evaluated the pathophysiology and associations between IBD and osteoporosis. Although corticosteroids contribute to the risk of low bone mineral density, osteoporosis and fractures, older age, female gender, smoking, and family history of fracture have been shown to contribute. Additionally, intestinal inflammation affects bone resorption and formation through proinflammatory cytokines such as tumor necrosis factor-a, interleukin-1, and interleukin-6 further accelerating bone loss. Little information is available on standardizing screening or treatment. It is important to recognize the risk factors that are associated with IBD and osteoporosis to identify the patient population at risk and initiate treatment/prevention strategies early. Treatment can include calcium, vitamin D, or bisphosphonates. Some studies showed benefit of treating the underlying IBD to improve bone mineral density.     

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...     

Insights on the impact of diet‐mediated microbiota alterations on immunity and diseases

The intestinal tract is inhabited by a large and diverse community of bacteria collectively referred to as the gut microbiota. The intestinal microbiota is composed by 500‐1000 distinct species, and alterations in its composition are associated with a variety of diseases including obesity, diabetes, and inflammatory bowel disease (IBD). Importantly, microbiota transplantation from diseased patients or mice (IBD, metabolic syndrome, etc.) to germ‐free mice was found to be sufficient to transfer some aspects of disease phenotypes, indicating that altered microbiota is playing a direct role in those particular conditions. Moreover, it is now well admitted that the intestinal microbiota is involved in shaping and maturating the immune system, with for example the observation that germ‐free animals harbor a poorly developed intestinal immune system and that some single bacteria species, such as segmented filamentous bacteria (SFB), are sufficient to induce the expansion of Th17 cells (CD4⁺ T helper cells producing IL‐17). We will present herein an overview of the interactions occurring between the intestinal microbiota and the immune system, and we will discuss how a dietary‐induced disruption of the intestinal environment may influence transplantation outcomes.     

肠道微生物与骨质疏松症的相关性研究进展

骨质疏松症作为骨骼退化性疾病，严重影响患者的生命质量，并给患者带来一定的经济和心理压力。近年来，肠道微生物作为被遗忘的“器官”逐渐成为研究热点，最近研究发现肠道微生物和骨质疏松症有着很高的相关性。笔者对最近有关肠道微生物和骨质疏松症的研究成果进行综述，希望为防治骨质疏松症提供新的研究靶点，为临床治疗提供新的思路。     

Inflammatory bowel diseases as secondary causes of osteoporosis

Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is associated with an increased risk of osteoporosis and bone fractures. Initial studies suggested very high rates of osteoporosis in IBD, but more recent studies have suggested that bone mineral density (BMD) is often normal in patients with IBD and typically changes little over time. Nonetheless, IBD is associated with an increased risk of fractures. Doctors managing patients with IBD must consider a variety of risk factors, not just BMD measurements, in assessing fracture risk. Advances have been made in exploring the pathogenesis of osteoporosis in IBD. The evolution of knowledge regarding receptor for activated factor of nuclear factor κB (RANK), its ligand RANKL, and osteoprotegerin (OPG), which serves as a decoy receptor, has enhanced the understanding of both osteoporosis and T-cell immunobiology. Recent clinical studies in patients with IBD have revealed that serum OPG levels may be elevated and inflamed intestinal tissue secretes increased amounts of OPG. It is suspected that OPG levels are elevated as a counterregulatory response to low BMD, as serum OPG levels in IBD have been found to be inversely associated with BMD. Finally, in animal models of IBD, exogenous OPG has reversed both the osteopenia and the enterocolitis, suggesting that it may have a therapeutic role in human IBD.     

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。     

肠道菌群：绝经后骨质疏松防治新靶点

绝经后骨质疏松是一类由雌激素缺乏引起的,以骨量减少和骨微结构破坏为特点的骨骼疾病,可诱发脆性骨折的发生率增加。绝经后骨质疏松因其较高的发病率和严重的并发症受到越来越多的关注。目前绝经后骨质疏松的治疗药物存在诸多副作用,部分药物甚至对器官、系统造成严重损害,因此亟待寻求一条新的安全有效的治疗途径。肠道菌群是定植在人体肠道内的微生物总集,而益生菌是由肠道有益菌组成的膳食或药物补剂。近年来多项研究表明,肠道菌群和机体正常骨改建与骨代谢疾病的发生息息相关,并且益生菌在部分骨代谢疾病治疗中已初步展现了较好疗效,提示肠道菌群可作为绝经后骨质疏松防治的潜在靶点并且益生菌的应用作为绝经后骨质疏松新治疗方法的可能性。本文通过对肠道菌群与绝经后骨质疏松的相关研究进行综述,归纳总结了肠道菌群与绝经后骨质疏松发生发展的相关性以及益生菌对其的治疗效果,并从肠道菌群多样性、肠道上皮屏障功能以及机体免疫系统调控3方面探讨肠道菌群、雌激素和益生菌在绝经后骨质疏松的致病与治疗过程中的相关作用机制。     

The gut microbiota regulates bone mass in mice

The gut microbiota modulates host metabolism and development of immune status. Here we show that the gut microbiota is also a major regulator of bone mass in mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced number of osteoclasts per bone surface compared with conventionally raised (CONV-R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone mass. Furthermore, GF mice have decreased frequency of CD4(+) T cells and CD11b(+) /GR 1 osteoclast precursor cells in bone marrow, which could be normalized by colonization. GF mice exhibited reduced expression of inflammatory cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut microbiota regulates bone mass in mice, and we provide evidence for a mechanism involving altered immune status in bone and thereby affected osteoclast-mediated bone resorption. Further studies are required to evaluate the gut microbiota as a novel therapeutic target for osteoporosis.     

Intestinal microbiota: a potential target for the treatment of postmenopausal osteoporosis

Postmenopausal osteoporosis(PMO) is a prevalent metabolic bone disease characterized by bone loss and structural destruction, which increases the risk of fracture in postmenopausal women. Owing to the high morbidity and serious complications of PMO, many efforts have been devoted to its prophylaxis and treatment. The intestinal microbiota is the complex community of microorganisms colonizing the gastrointestinal tract. Probiotics, which are dietary or medical supplements consisting of beneficial intestinal bacteria, work in concert with endogenous intestinal microorganisms to maintain host health. Recent studies have revealed that bone loss in PMO is closely related to host immunity, which is influenced by the intestinal microbiota. The curative effects of probiotics on metabolic bone diseases have also been demonstrated. The effects of the intestinal microbiota on bone metabolism suggest a promising target for PMO management.This review seeks to summarize the critical effects of the intestinal microbiota and probiotics on PMO, with a focus on the molecular mechanisms underlying the pathogenic relationship between bacteria and host, and to define the possible treatment options.