肠道菌群与2型糖尿病相关性的研究进展

肠道菌群是人体肠道微生态的重要组成部分,以多种途径影响宿主的代谢与生理功能,通过调节肠道菌群结构与多样性,改善慢性疾病的发生发展已成为国内外的研究热点。本研究归纳总结了近年来肠道菌群影响2型糖尿病的主要途径,为阐明肠道菌群与2型糖尿病的相关性以及基于肠道菌群靶点的药物研制和临床治疗提供新的思路。     

肠道菌群与肠易激综合征相关研究进展

肠易激综合征(irritable bowel syndrome,IBS)是一种功能性肠病,目前已有研究表明IBS的致病机制、症状的产生和持续时间可能与肠道菌群失调有关,且不同IBS亚型患者体内的肠道菌群种类有差异。IBS的发病机制尚不完全清楚,临床表现存在较大的个体差异。IBS的诊断和治疗尚未形成统一的标准。但已经有较多研究提示IBS可能与胃肠道动力、内脏高敏感性、肠道免疫反应和模式识别受体等密切相关,并且可以通过益生菌、益生元、抗生素、粪菌移植和饮食习惯等调节肠道菌群的失调,从而改善IBS的症状。这也为未来治疗IBS提供了新的思路。本文就肠道菌群的概况、IBS患者肠道菌群的特点、肠道菌群失衡导致IBS发病的可能机制以及IBS肠道菌群的相关治疗方法的研究进展作一综述。     

质子泵抑制剂对慢性肝病患者肠道微生态的影响

目的探究质子泵抑制剂(PPIs)对慢性肝病患者肠道微生态的影响。方法选取郑州市第六人民医院2018年12月至2019年3月诊断及拟行PPIs治疗的慢性肝病患者31名,使用奥美拉唑进行治疗,20 mg/次,2次/d,疗程4周,检测治疗前后肠道菌群的构成。结果治疗前后患者肠道菌群构成差异显著:治疗后患者肠道菌群在Shannon指数(4.61±0.62 vs 5.01±0.83;t=2.889,P=0.005)、Simpson指数(0.89±0.09 vs 0.95±0.11;t=3.159,P=0.002)显著低于治疗前;治疗前患者肠道菌群中Coriobacteriaceae、Eggerthella、Ruminococcus、Anaerotruncus、Dorea、Turicibacter、Paraprevotella的相对丰度显著高于治疗后,治疗后肠道菌群中Veillonellaceae、Campylobacter、Haemophilus、Streptococcus、Streptococcaceae、Lactobacillus、Lactobacillaceae的相对丰度显著高于治疗前(均P<0.05)。结论PPIs可改变慢性肝病患者肠道菌群的构成。     

肠道菌群与胆汁酸代谢在代谢相关脂肪性肝病的发生发展中的作用CSCD

代谢相关脂肪性肝病(metabolic-dysfunction-associated fatty liver disease,MAFLD)已成为我国慢性肝病的主要病因之一,其发病率呈逐年上升趋势。MAFLD是代谢综合征累及肝脏的表现,其发生发展与肠道菌群失调和代谢功能障碍等密切相关。由于发病机制尚不明确,目前依旧缺乏有效的药物治疗方法。肠道菌群与胆汁酸代谢密切相关,胆汁酸可靶向法尼醇X受体(farnesoid X receptor,FXR)信号通路负反馈调控肠道菌群,同时肠道菌群通过一系列复杂的生化反应影响胆汁酸代谢。大量研究发现MAFLD的免疫应答受损及全身低度慢性炎症可导致胆汁酸代谢紊乱。此外,MAFLD常伴随肠道菌群失调。本文就肠道菌群与胆汁酸代谢在MAFLD发生发展中的作用作一综述,以期探寻治疗MAFLD潜在的新的靶点。     

微生物在精神分裂症发病机制的研究现状

脑和肠道微生物群之间的相互作用逐渐被揭示。目前已经提出脑-肠轴失调和异常与各种中枢神经系统疾病有关。精神分裂症是一种病因不明的严重精神障碍。最近研究表明,肠道微生物的组成和数量变化会通过肠道菌群-肠-脑轴影响人类的认知和社会行为,这意味着肠道菌群在精神分裂症患者中可能起着重要的作用,并有望成为精神分裂症新的治疗靶点。本文综述了肠道菌群与精神分裂症相关性的研究进展,为预防和治疗精神分裂症等精神障碍类疾病提供了理论依据。     

肠道梭菌属与2型糖尿病的相关性研究进展

摘要：随着经济社会的发展和人类生活水平的提高,2型糖尿病及其慢性并发症不仅严重影响了患者自身的生活质量,而且也给其家庭和社会带来了沉重的负担,已逐渐成为全球突出的社会问题。如果人体内肠道菌群的结构和功能发生紊乱,则可能引起2型糖尿病的发生,因此肠道菌群成为备受关注的研究对象。相关文献指出肠道菌群中的梭菌属与肠黏膜完整性、内脏脂肪、免疫稳态、能量代谢、肠蠕动有关。本文总结了梭菌属的生物学特性、在机体内的生理功能及与2型糖尿病之间的相关性,旨在为进一步研究肠道梭菌属与2型糖尿病间的关系提供参考。     

微生态制剂对慢性肝衰竭患者肠道菌群的影响

目的探讨微生态调节剂双歧杆菌三联活菌对慢性肝衰竭患者肠道菌群的影响。方法根据治疗方法不同将46例慢性肝衰竭患者随机分为治疗组和对照组各23例,两组均给予慢性肝衰竭常规治疗,治疗组在上述基础上给予双歧杆菌三联活菌胶囊,210mg／粒,每次2粒,2次／d,疗程2周。观察治疗前后两组患者的肠道菌群菌落计数变化及血清总胆红素（TBiL）、凝血酶原时间（PT）变化。结果两组患者在实验前肠道菌群、TBiL、PT比较差异均无统计学意义（P〉0．05）。治疗2周后,对照组患者治疗前后肠道菌群无明显变化（P〉0．05）,TBiL、PT有所下降但不显著,治疗组患者的肠球菌、双歧杆菌、乳杆菌以及酵母样真菌的菌落数均较治疗前明显增加,TBiL、PT较前明显好转（P〈0．05）。结论口服双歧杆菌三联活菌制剂可以促进慢性肝衰竭患者肠道正常菌群的恢复及改善肝功能。     

肠道菌群在2型糖尿病并发抑郁症中的作用探析

抑郁症作为2型糖尿病常见并发症,不仅严重危害人体的健康,而且增加了疾病的治疗难度。临床中对于本病的治疗通常将二者分开,采用降糖与抗抑郁联合的方法,却忽视了抑郁症作为2型糖尿病的并发症,两者必定存在内在联系。研究表明,2型糖尿病患者肠道菌群存在明显失衡,而肠道菌群与抑郁症的发生密切相关,因此肠道菌群可能在2型糖尿病并发抑郁症中起着重要作用,本文通过论述三者的关系,认为肠道菌群失调可能是糖尿病并发抑郁症的关键因素,提出肠道菌群可能是干预2型糖尿病并发抑郁的新靶点,以期为2型糖尿病并发抑郁症的治疗提供新的途径。     

肠道菌群在中药研究中的应用概况

自上个世纪以来,随着肠道菌群的相关性研究日益增多,人们发现肠道菌群与人类健康密切相关。近年来,肠道菌群在中药的研究方面也引发了科学家们激烈的讨论。本文主要对肠道菌群在中药研究中的相互作用、相互影响进行综述,阐述了较为前沿的肠道菌群的研究方法。同时对近十年来关于肠道菌群的相关文献的不同及进步进行思考和展望。该综述为预防、治疗肠道菌群失调开辟新的思路。     

肠道菌群与非酒精性脂肪肝病相关性研究进展

近年来关于肠道菌群与非酒精性脂肪肝疾病关系的研究越来越多。非酒精性脂肪肝是一种无过量饮酒史,肝内脂肪过量堆积的慢性疾病。生理解剖结构上的"肠-肝轴"表明肠道和肝脏有着密不可分的关系。肠道菌群一般情况下处于动态平衡,可以维持肠道正常生理功能。肠道菌群可通过改善肠道通透性、干预脂质代谢、产生内源性乙醇和产生短链脂肪酸等来影响非酒精性脂肪肝疾病的发生与发展。临床上对于治疗非酒精性脂肪肝没有确切的药物,增加有益肠道菌群的因素,如益生元、益生菌等能够调节肠道的微环境,这为非酒精性脂肪肝疾病的治疗开辟了新的方向。     

Evidence-based hydro- and balneotherapy in Hungary—a systematic review and meta-analysis

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis.     

Association of the IL-6 -174G/C gene polymorphism with knee osteoarthritis in a Thai population

Osteoarthritis is a chronic progressive degenerative joint disease characterized by age-related regressive change in articular cartilage. A single nucleotide polymorphism has been described at position -174 of the interleukin-6 (IL-6) promoter region, leading to three possible genotypes, GG, GC, and CC. We investigated a possible association of the IL-6 -174G/C gene polymorphism with knee osteoarthritis in a Thai population. Genotype distributions and allelic frequencies of the IL-6 -174G/C polymorphism were investigated in 115 knee osteoarthritis patients and 100 healthy controls. Genotyping was performed using PCR-RFLP. The genotype distribution of IL-6 was 79 GG, 36 GC, 0 CC in knee osteoarthritis patients and 88 GG, 12 GC, 0 CC in controls. The frequency of the GC genotype in subjects with knee osteoarthritis was higher than in controls (P< 0.001). Logistic regression analysis showed that the GC genotype was independently associated with increased risk of knee osteoarthritis (odds ratio = 3.3, 95% confidence interval = 1.6-6.9, P = 0.001). These findings suggest that the -174G/C polymorphism of the IL-6 gene promoter plays a role in the pathogenesis of knee osteoarthritis.     

Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee – A randomized double blind placebo controlled trial

Osteoarthritis is a common, chronic, progressive, skeletal, degenerative disorder, which commonly affects the knee joint. Boswellia serrata tree is commonly found in India. The therapeutic value of its gum (guggulu) has been known. It posses good anti-inflammatory, anti-arthritic and analgesic activity. A randomized double blind placebo controlled crossover study was conducted to assess the efficacy, safety and tolerability of Boswellia serrata Extract (BSE) in 30 patients of osteoarthritis of knee, 15 each receiving active drug or placebo for eight weeks. After the first intervention, washout was given and then the groups were crossed over to receive the opposite intervention for eight weeks. All patients receiving drug treatment reported decrease in knee pain, increased knee flexion and increased walking distance. The frequency of swelling in the knee joint was decreased. Radiologically there was no change. The observed differences between drug treated and placebo being statistically significant, are clinically relevant. BSE was well tolerated by the subjects except for minor gastrointestinal ADRs. BSE is recommended in the patients of osteoarthritis of the knee with possible therapeutic use in other arthritis.     

Stem cell application for osteoarthritis in the knee joint: A minireview

Knee osteoarthritis is a chronic, indolent disease that will affect an ever increasing number of patients, especially the elderly and the obese. It is characterized by degeneration of the cartilage substance inside the knee which leads to pain, stiffness and tenderness. By some estimations in 2030, only in the United States, this medical condition will burden 67 million people. While conventional treatments like physiotherapy or drugs offer temporary relief of clinical symptoms, restoration of normal cartilage function has been difficult to achieve. Moreover, in severe cases of knee osteoarthritis total knee replacement may be required. Total knee replacements come together with high effort and costs and are not always successful. The aim of this review is to outline the latest advances in stem cell therapy for knee osteoarthritis as well as highlight some of the advantages of stem cell therapy over traditional approaches aimed at restoration of cartilage function in the knee. In addition to the latest advances in the field, challenges associated with stem cell therapy regarding knee cartilage regeneration and chondrogenesis in vitro and in vivo are also outlined and analyzed. Furthermore, based on their critical assessment of the present academic literature the authors of this review share their vision about the future of stem cell applications in the treatment of knee osteoarthritis.     

A proposed model of naturally occurring osteoarthritis in the domestic rabbit

Osteoarthritis affects one in eight American adults over the age of 25 y and is a leading cause of chronic disability in the US. Translational research to investigate treatments for this naturally occurring joint disease requires an appropriate animal model. The authors conducted a retrospective study to assess the potential of naturally occurring osteoarthritis in the domestic rabbit as a model of the human disease. Analysis of radiographic images showed that the presence and severity of osteoarthritis were significantly influenced by both age and body weight. The most commonly affected joints were the knee and the hip. The findings reported here suggest that the rabbit is an excellent model of spontaneously arising osteoarthritis that may be useful in translational research pertaining to the human disease.     

富血小板血浆注射治疗在膝骨关节炎中的应用进展

富血小板血浆(platelet-rich plasma，PRP)由于富含多种活性生长因子，能够刺激软骨细胞增殖，促进软骨前体细胞增殖、迁移、向软骨细胞分化，促进胶原蛋白合成以及抑制软骨的炎性反应和退变，提供有利于组织修复的内环境，延缓病情进展。近年来PRP注射治疗已成为治疗与骨关节炎(osteoarthritis，OA)相关疾病的新型选择，并且疗效显著。为了进一步提高其效用，PRP注射治疗不仅在关节腔内进行，还可在软骨下骨内进行注射。软骨下骨的病变会加速软骨损耗，故有必要将软骨下骨也当作OA众多发病机制和病理过程的关键因素之一。根据PRP的生物特效以及PRP注射治疗在膝骨关节炎(knee osteoarthritis，KOA)中应用的研究进展进行了综述，同时对软骨下骨内PRP注射治疗KOA的研究进行了展望，以期为KOA的治疗提供更加有效的方法。     

Changes in pain catastrophizing predict later changes in fibromyalgia clinical and experimental pain report: cross-lagged panel analyses of dispositional and situational catastrophizing

Introduction

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be important in the development of inflammatory models of rheumatoid arthritis and there is encouraging data that its blockade may have clinical relevance in patients with rheumatoid arthritis. The aims of the current study were to determine whether GM-CSF may also be important for disease and pain development in a model of osteoarthritis.

Methods

The role of GM-CSF was investigated using the collagenase-induced instability model of osteoarthritis. We studied both GM-CSF-/- mice and wild-type (C57BL/6) mice treated prophylactically or therapeutically with a monoclonal antibody to GM-CSF. Disease development (both early and late) was evaluated by histology and knee pain development was measured by assessment of weight distribution.

Results

In the absence of GM-CSF, there was less synovitis and matrix metalloproteinase-mediated neoepitope expression at week 2 post disease induction, and less cartilage damage at week 6. GM-CSF was absolutely required for pain development. Therapeutic neutralization of GM-CSF not only abolished the pain within 3 days but also led to significantly reduced cartilage damage.

Conclusions

GM-CSF is key to the development of experimental osteoarthritis and its associated pain. Importantly, GM-CSF neutralization by a therapeutic monoclonal antibody-based protocol rapidly and completely abolished existing arthritic pain and suppressed the degree of arthritis development. Our results suggest that it would be worth exploring the importance of GM-CSF for pain and disease in other osteoarthritis models and perhaps clinically for this form of arthritis.     

Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development

Introduction

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be important in the development of inflammatory models of rheumatoid arthritis and there is encouraging data that its blockade may have clinical relevance in patients with rheumatoid arthritis. The aims of the current study were to determine whether GM-CSF may also be important for disease and pain development in a model of osteoarthritis.

Methods

The role of GM-CSF was investigated using the collagenase-induced instability model of osteoarthritis. We studied both GM-CSF-/- mice and wild-type (C57BL/6) mice treated prophylactically or therapeutically with a monoclonal antibody to GM-CSF. Disease development (both early and late) was evaluated by histology and knee pain development was measured by assessment of weight distribution.

Results

In the absence of GM-CSF, there was less synovitis and matrix metalloproteinase-mediated neoepitope expression at week 2 post disease induction, and less cartilage damage at week 6. GM-CSF was absolutely required for pain development. Therapeutic neutralization of GM-CSF not only abolished the pain within 3 days but also led to significantly reduced cartilage damage.

Conclusions

GM-CSF is key to the development of experimental osteoarthritis and its associated pain. Importantly, GM-CSF neutralization by a therapeutic monoclonal antibody-based protocol rapidly and completely abolished existing arthritic pain and suppressed the degree of arthritis development. Our results suggest that it would be worth exploring the importance of GM-CSF for pain and disease in other osteoarthritis models and perhaps clinically for this form of arthritis.     

根际微生物与植物再植病的发生发展关系

植物再植病严重危害农作物的生长发育,形成原因复杂,最新的研究显示它与根际微生态的变化相关,其中主要涉及根际微生物菌群结构的变化。现代高通量测序技术的迅速推广使得根际微生物和再植病间关系成为新的研究热点;本文根据国内外植物再植病病因、根际土壤微生物多样性以及它们与植物生长发育关系等多方面的研究成果,综合分析植物再植病与根际微生物间的关系,以期从根际微生物种群动态变化的角度认识植物再植病的病因并为防治提供新的思路。     

基于机器学习的肠道菌群数据建模与分析研究综述

人体肠道菌群与人类的健康和疾病存在密切关系,对肠道菌群的宏基因组数据进行建模和分析,在疾病预测及诊断相关领域科学研究和社会应用方面均具有重要意义。本文从大数据分析和机器学习的角度,对人体肠道菌群数据的建模、分析和预测算法的原理、过程以及典型研究应用实例进行综述,以期推动肠道菌群分析相关研究发展以及探索结合机器学习算法进行肠道菌群分析的有效方式,同时也为开发基于肠道菌群数据的新型诊疗手段提供借鉴,推动我国精准医疗事业发展。