Specific alterations in gut microbiota in patients with chronic kidney disease: an updated systematic review

BackgroundEmerging evidence demonstrates that gut dysbiosis is implicated in the pathogenesis of chronic kidney disease (CKD) with underlying mechanisms involving mucosal and/or systematic immunity or metabolic disorders. However, the profile of gut microbiota in patients with CKD has not been completely explored.MethodsDatabases from their date of inception to 31 March 2020 were systematically searched for case-control or cross-sectional studies comparing the gut microbial profiles in adult patients with CKD or end-stage renal disease (ESRD) with those in healthy controls. Quantitative analysis of alterations in gut microbial profiles was conducted.ResultsTwenty-five studies with a total of 1436 CKD patients and 918 healthy controls were included. The present study supports the increased abundance of, phylum Proteobacteria and Fusobacteria, genus Escherichia_Shigella, Desulfovibrio, and Streptococcus, while lower abundance of genus Roseburia, Faecalibacterium, Pyramidobacter, Prevotellaceae_UCG-001, and Prevotella_9 in patients with CKD; and increased abundance of phylum Proteobacteria, and genus Streptococcus and Fusobacterium, while lower abundance of Prevotella, Coprococcus, Megamonas, and Faecalibacterium in patients with ESRD. Moreover, higher concentrations of trimethylamine-N-oxide and p-cresyl sulfate and lower concentrations of short-chain fatty acids were observed. Gut permeability in patients with CKD was not determined due to the heterogeneity of selected parameters.ConclusionsSpecific alterations of gut microbial parameters in patients with CKD were identified. However, a full picture of the gut microbiota could not be drawn from the data due to the differences in methodology, and qualitative and incomplete reporting of different studies.     

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。     

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。     

Relationship between gut microbiota and vascular calcification in hemodialysis patients

IntroductionVascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated and unclear. Uremic toxins produced by gut microbiota can promote VC. This study aims to identify the differences in gut microbiota between the different VC groups and the main bacteria associated with VC in hemodialysis (HD) patients in an attempt to open up new preventive and therapeutic approaches and define the probable mechanism for VC in HD patients in the future.MethodsA total of 73 maintenance HD patients were enrolled in this cross-sectional study. According to the abdominal aortic calcification (AAC) scores, the participants were divided into the high AAC score group and the low AAC score group. High-throughput sequencing of the gut microbiota was performed and the results were evaluated by alpha diversity, beta diversity, species correlation, and model predictive analyses.ResultsThe prevalence of VC was 54.79% (40/73) in the study. The majority of phyla in the two groups were the same, including Firmicutes, Actinobacteriota, Proteobacteria, and Bacteroidota. The microbial diversity in the high AAC score group had a decreasing trend (p = 0.050), and the species abundance was significantly lower (p = 0.044) than that in the low AAC score group. The HD patients with high AAC scores showed an increased abundance of Proteobacteria and decreased abundances of Bacteroidota and Synergistota at the phylum level; increased abundances of Escherichia-Shigella, Ruminococcus_gnavus_group, and Lactobacillus; and decreased abundances of Ruminococcus and Lachnospiraceae_NK4A136_group at the genus level (p<0.05). Escherichia-Shigella and Ruminococcus_gnavus_group were positively correlated with VC, and Ruminococcus, Adlercreutzia, Alistipes, and norank_f__Ruminococcaceae were negatively correlated with VC. Escherichia-Shigella had the greatest influence on VC in HD patients, followed by Ruminococcus and Butyricimonas.ConclusionsOur results provide clinical evidence that there was a difference in gut microbiota between the different VC groups in HD patients. Escherichia–Shigella, a lipopolysaccharide (LPS)-producing bacterium, was positively correlated with VC and had the greatest influence on VC. Ruminococcus, a short-chain fatty acid (SCFA)-producing bacterium, was negatively correlated with VC and had the second strongest influence on VC in HD patients. The underlying mechanism is worth studying. These findings hint at a new therapeutic target.     

肠道菌群对骨代谢作用机制的研究进展

肠道菌群（gut microbiota, GM）是人体内密度最大的微生物群落,能影响机体的生理病理状态。本文利用中国知网、PubMed等数据库,以GM、骨代谢、骨质疏松等为关键词,检索了近20年国内外相关文献,发现GM可能通过以下途径影响骨代谢：（1）影响钙的吸收、调节宿主的免疫系统和中枢神经系统等;（2）调节其代谢产物（如短链脂肪酸、次胆汁酸、吲哚类衍生物和多胺等）的含量;（3）调节雌激素、胰岛素样生长因子1、5-羟色胺等激素的水平。临床研究表明,粪便微生物群移植、补充益生菌和益生元或调节饮食结构可改善GM的组成,能抑制骨量的下降。因此,GM及其代谢产物可能成为骨质疏松症等骨代谢疾病的防治新靶点。     

基于16S rRNA高通量测序技术分析I型骨质疏松大鼠肠道菌群结构变化

目的 探讨I型骨质疏松大鼠肠道菌群的结构变化。方法 采用去势法建立I型骨质疏松大鼠模型（n=24）：雌性SD大鼠随机分为4组（n=6）,实验动物自由进食水,12 h光照周期。分别在去势前和去势后4、8、12周共4个时间点,采用直接收集法采集大鼠粪便。利用16S rRNA高通量肠菌基因测序技术,在phylum（门）,class（纲）,order（目）,family（科）,genus（属）,species（种）级别分析肠道菌群的变化规律。结果 厚壁菌门与拟杆菌门是肠道菌群的主要构成肠菌,无论在去势前或去势后,二者含量之和均超过肠道菌群总量的90%。厚壁菌门含量在去势后下降并且持续到术后8周,其含量在术后12周显著增加（P<0.05）;拟杆菌门的含量变化趋势与此相反。另外,在纲、目级别的物种差异变化趋势较为一致。普雷沃氏菌属、Odoribacter 含量在术后12周明显降低（P<0.05）,而螺杆菌属与Alistipes在术后12周含量显著增多（P<0.05）。在种级别的分类中,白色瘤胃球菌在术后12周显著增多（P<0.05）,而单形拟杆菌含量显著降低（P<0.05）。结论 I型骨质疏松大鼠的肠道菌群在不同分类级别的结构组成上发生了显著性改变,为研究肠道菌群和骨质疏松症的关系提供理论依据。     

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。     

Curcumin modulates gut microbiota and improves renal function in rats with uric acid nephropathy

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 μmol/L vs. 325.60 ± 18.65 μmol/L, p < 0.001), serum creatinine (66.20 ± 11.88 μmol/L vs. 182.20 ± 8.87 μmol/L, p < 0.001) and BUN level (13.33 ± 3.16 mmol/L vs. 36.04 ± 6.60 mmol/L, p < 0.001). The treatment group also displayed attenuated renal pathological lesions and metabolic endotoxemia (25.60 ± 5.90 ng/mL vs. 38.40 ± 4.98 ng/mL, p < 0.01), and improved tightly linked proteins expression. Besides, curcumin altered the gut microbiota structure in UAN rats. More specifically, curcumin treatment protected against the overgrowth of opportunistic pathogens in UAN, including Escherichia-Shigella and Bacteroides, and increased the relative abundance of bacteria producing short‐chain fatty acids (SCFAs), such as Lactobacillus and Ruminococcaceae. These results suggest that curcumin could modulate gut microbiota, fortify the intestinal barrier, attenuate metabolic endotoxemia, and consequently protect the renal function in UAN rats.     

肠道菌群介导贞术调脂胶囊抑制去势小鼠骨丢失的机制研究

目的 基于肠道菌群的变化,探讨贞术调脂胶囊（FTZ）抑制去卵巢（OVX）小鼠骨丢失的作用机制。方法选取18只11周C57BL6/J雌性小鼠,平均分为假手术组（SHAM组）、OVX组和FTZ组。FTZ组在OVX基础上给予FTZ[1.55 g/(kg·d）]灌胃,SHAM组和OVX组以等剂量0.9%氯化钠溶液灌胃,12周后收集小鼠左侧股骨、血清和粪便标本。左侧股骨行Micro-CT扫描;采用ELISA法检测血清中TNF-α、IL-10、IL-6、LPS和TRACP5b的含量;末次灌胃结束24 h后收集小鼠粪便,提取并检测粪菌总DNA,利用16S rRNA高通量肠菌基因测序技术,对标本中的细菌16S rRNA 基因V3-V4可变区进行定性分析和OUT分析。结果 与SHAM组相比,OVX组BV/TV、Tb.N、BMD和IL-10均显著性降低(P＜0. 05),Tb.Sp、TNF-α、IL-6、LPS和TRACP5b显著性增高（P＜0. 05）;与OVX组相比,FTZ组Tb.N和IL-10显著性增高（P＜0. 05）,Tb.Sp、TNF-α、IL-6和TRACP5b显著性降低（P＜0. 05）。在门水平,OVX组Firmicutes/Bacteroidota（F/B）率较SHAM组有增高趋势（P=0.310）,但无显著性差异,而与OVX组相比,FTZ组F/B率显著性降低（P=0.002）。在属水平,与SHAM组相比,Faecalibaculum和Coriobacteriaceae_UCG-002丰度在OVX组中显著减少（P=0.030,P=0.005）,Lachnoclostridium丰度在OVX组中显著增加（P=0.037）,而与OVX组相比,FTZ组Faecalibaculum和Coriobacteriaceae_UCG-002丰度显著增加（P =0.045,P=0.005）,Lachnoclostridium丰度显著减少（P=0.013）。结论 FTZ能够延缓去势小鼠骨量丢失,其机制可能是通过调节肠道菌群中Faecalibaculum、Coriobacteriaceae_UCG-002和Lachnoclostridium丰度实现的,且同时抑制炎性反应。     

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。     

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。     

益肠通秘汤通过调节肠道菌群结构改善小鼠便秘

目的：探讨益肠通秘汤对便秘小鼠肠道组织屏障及肠道菌群结构的影响。方法：取8周龄Balb/c小鼠40只,采用皮下注射洛哌丁胺方法建立便秘模型。40只小鼠随机分为正常组、模型组、益肠通秘汤组（14 g/kg）和枸橼酸莫沙必利（莫沙必利）组（5 g/kg）,每组10只。模型组、益肠通秘汤组和莫沙必利组连续每日皮下注射洛哌丁胺（10 mg/kg）2周建立便秘模型。观察各组小鼠一般情况、粪便参数及肠道推进率等。用H&E染色、免疫组化方法分别检测结肠组织的病理学改变和Claudin-1表达水平,采用16S r DNA技术检测肠道菌群变化。结果：与正常组相比,模型组小鼠体重持续下降,粪便颗粒数、粪便含水量及肠道推进率降低（P<0.05）,结肠肌层变薄,杯状细胞数量减少,Claudin-1表达量降低;益肠通秘汤干预后体重回升,粪便颗粒数、粪便含水量及肠道推进率趋近正常,结肠组织结构破坏减轻,Claudin-1表达增加;菌群测序结果显示,益肠通秘汤在门水平抑制了Firmicutes的上调和Bacteroidetes的下调,属水平降低了Bacteroides的相对丰度,增加了Ruminoco...     

Masked Uncontrolled Hypertension in CKD

Masked uncontrolled hypertension (MUCH) is diagnosed in patients treated for hypertension who are normotensive in the clinic but hypertensive outside. In this study of 333 veterans with CKD, we prospectively evaluated the prevalence of MUCH as determined by ambulatory BP monitoring using three definitions of hypertension (daytime hypertension ≥135/85 mmHg; either nighttime hypertension ≥120/70 mmHg or daytime hypertension; and 24-hour hypertension ≥130/80 mmHg) or by home BP monitoring (hypertension ≥135/85 mmHg). The prevalence of MUCH was 26.7% by daytime ambulatory BP, 32.8% by 24-hour ambulatory BP, 56.1% by daytime or night-time ambulatory BP, and 50.8% by home BP. To assess the reproducibility of the diagnosis, we repeated these measurements after 4 weeks. Agreement in MUCH diagnosis by ambulatory BP was 75–78% (κ coefficient for agreement, 0.44–0.51), depending on the definition used. In contrast, home BP showed an agreement of only 63% and a κ coefficient of 0.25. Prevalence of MUCH increased with increasing clinic systolic BP: 2% in the 90–110 mmHg group, 17% in the 110–119 mmHg group, 34% in the 120–129 mmHg group, and 66% in the 130–139 mmHg group. Clinic BP was a good determinant of MUCH (receiver operating characteristic area under the curve 0.82; 95% confidence interval 0.76–0.87). In diagnosing MUCH, home BP was not different from clinic BP. In conclusion, among people with CKD, MUCH is common and reproducible, and should be suspected when clinic BP is in the prehypertensive range. Confirmation of MUCH diagnosis should rely on ambulatory BP monitoring.