Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in β-lactoglobulin-induced allergic mice model

Objectivesβ-lactoglobulin (β-Lg)-sensitized mice model was employed to investigate the correlation between Lactobacillus acidophilus KLDS 1.0738 (Lap KLDS 1.0738) modulating gut microbiota and inducting Toll-like receptors (TLRs) expression.MethodsThe alterations of mice fecal microbiota were analyzed by 16S rRNA gene sequencing. The serum cytokines production and TLR4/NF-κB mRNA expression in the colon tissues were measured by ELISA kit and quantitative RT-PCR, respectively.ResultsThe results showed that Lap KLDS 1.0738 pretreatment attenuated β-Lg-induced hypersensitivity, accompanied with a diminished expression of TLR4/NF-κB signaling. Moreover, oral administration of Lap KLDS 1.0738 improved the richness and diversity of fecal microbiota, which was characterized by fewer Proteobacteria phylum and Helicobacteraceae family, and higher Firmicutes phylum and Lachnospiraceae family than allergic group. Notably, TLR4/NF-κB expression was positively correlated with the family of Helicobacteraceae in allergic group, but negatively correlated with the family of Lachnospiraceae, Ruminococcaceae and anti-inflammatory cytokines level. A significant positive correlation was observed between TLR4/NF-κB expression and the production of histamine, total IgE and pro-inflammatory cytokines.ConclusionsIntake of Lap KLDS 1.0738 can influence the gut bacterial composition, which might result in recognizing TLRs signaling so as to inhibit allergic response.     

抗生素诱导的肠道菌群失调加重小鼠肺炎支原体感染

目的初步探讨抗生素诱导的肠道菌群失调对肺炎支原体(Mycoplasma pneumoniae,Mp)呼吸道感染的影响。方法C57BL/6J小鼠口服万古霉素和庆大霉素21 d后滴鼻感染Mp。实时荧光定量PCR(qPCR)分析抗生素处理前后小鼠粪便中5个主要菌门的菌量;qPCR检测感染后3 d和7 d肺组织中Mp载量;病理切片和HE染色分析肺组织炎症病理改变;流式细胞术分析小鼠脾脏T淋巴细胞分泌的IFN-γ和IL-4;间接ELISA检测Mp特异性IgM和IgG。结果口服万古霉素和庆大霉素后小鼠粪便中拟杆菌门菌量显著减少,厚壁菌门菌量增多,δ,γ变形杆菌门、放线菌门和软壁菌门菌量亦发生改变;口服抗生素小鼠感染Mp后3 d和7 d肺组织Mp载量和炎症病理评分增加,7 d小鼠脾淋巴细胞中分泌IFN-γ的CD4+T细胞减少。结论抗生素诱导的小鼠肠道菌群失调可加重Mp呼吸道感染。     

睡眠剥夺对限制能量平衡膳食的减重效果及肠道菌群丰度的影响

目的研究睡眠剥夺对单纯性肥胖患者限制能量平衡膳食（CRD）减重效果、生化指标及肠道菌群丰度变化的影响。 方法观察2018年9月至2019年11月徐州医科大学附属淮安医院肥胖门诊筛选的睡眠剥夺组（8例）及正常睡眠组（8例）的单纯性肥胖患者CRD干预12周前后身体形态指标、生化指标及肠道菌群特征的变化。采用单因素方差分析比较组间差异,配对样本t检验比较同组受试者减重前后指标的差异,采用Kruskal-Wallis检验比较肠道菌群组间差异,采用Spearman相关性分析分析临床指标及宿主菌群的相关性。 结果（1）CRD干预后睡眠剥夺组及正常睡眠组的体质量［（83.85±9.30）kg vs （85.88±8.76）kg;（79.23±14.52）kg vs （88.00±13.16）kg］、腰围［（98.60±6.76）cm vs（100.73±6.14）cm;（96.14±11.26）cm vs （101.61±8.52）cm］及基础代谢率［BMR,（1476.25±146.63）kcal vs（1501.75±149.36）kcal;（1427.00±228.02）kcal vs （1477.38±229.98）kcal］均较干预前下降,差异均具有统计学意义（t=2.898、3.895,P=0.023、0.006;t=3.694、3.103,P=0.008、0.017;t=3.599、5.994,P=0.009、0.001）。（2）睡眠剥夺组患者CRD干预后,体质量变化值［（2.02±1.97）kg vs （8.76±6.36）kg］、体脂肪量变化值［（0.55±1.93）kg vs （5.25±5.10）kg］、体脂肪面积变化值［（-3.25±14.41）cm² vs （36.13±48.94）cm²］、BMR变化值［（25.50±20.04）kcal vs （50.38±23.77）kcal］及总胆固醇变化值［（-0.06±0.37）mmol/L vs （0.77±0.76）mmol/L］均较正常睡眠组小,组间差异均具有统计学意义（t=2.424、1.692、6.102、0.702、3.802,P=0.013、0.029、0.047、0.040、0.014）;（3）2组干预前后的肠道菌群Alpha多样性未见明显差异,研究期间,正常睡眠组Mollicutes菌与BMR呈稳定负相关关系。 结论CRD干预能有效降低单纯性肥胖患者的体质量、腰围、BMR;睡眠剥夺可能在一定程度上减弱CRD的减重效果,影响血脂的代谢;单纯性肥胖人群CRD干预过程中,Mollicutes菌可能是影响CRD减重效果的原因之一。     

肠道菌群在自身免疫性疾病中的研究进展

自身免疫性疾病(autoimmune disease,AID)通过自身产生抗体,导致免疫耐受失衡,而引起的一系列慢性炎症反应,甚至对机体组织造成损伤。目前AID发病率逐渐升高,而其确切的发病机制尚不明确。肠道菌群作为人体最大的"免疫器官",参与机体代谢,形成肠粘膜屏障,维持免疫功能正常。随着对人体肠道菌群研究的深入,越...     

Resveratrol alleviates temporomandibular joint inflammatory pain by recovering disturbed gut microbiota

Patients with temporomandibular disorders (TMDs) often experience persistent facial pain. However, the treatment of TMD pain is still inadequate. In recent years, the disturbance of gut microbiota has been shown to play an important role in the pathogenesis of different neurological diseases including chronic pain. In the present study, we investigated the involvement of gut microbiota in the development of temporomandibular joint (TMJ) inflammation. Intra-temporomandibular joint injection of complete Freund's adjuvant (CFA) was employed to induce TMJ inflammation. Resveratrol (RSV), a natural bioactive compound with anti-inflammatory property, was used to treat the CFA-induced TMJ inflammation. We observed that CFA injection not only induces persistent joint pain, but also causes the reduction of short-chain fatty acids (SCFAs, including acetic acid, propionic acid and butyric acid) in the gut as well as decreases relevant gut bacteria Bacteroidetes and Lachnospiraceae. Interestingly, systemic administration of RSV (i.p.) dose-dependently inhibits CFA-induced TMJ inflammation, reverses CFA-caused reduction of SCFAs and these gut bacteria. Moreover, CFA injection causes blood–brain barrier (BBB) leakage, activates microglia and enhances tumor necrosis factor alpha (TNFα) release in the spinal trigeminal nucleus caudalis (Sp5C). The RSV treatment restores the BBB integrity, inhibits microglial activation and decreases the release of TNFα in the Sp5C. Furthermore, fecal microbiota transplantation with feces from RSV-treated mice significantly diminishes the CFA-induced TMJ inflammation. Taken together, our results suggest that gut microbiome perturbation is critical for the development of TMJ inflammation and that recovering gut microbiome to normal levels could be a new therapeutic approach for treating such pain.     

高通量测序分析重度寻常痤疮患者和健康人肠道菌群差异

目的 利用高通量测序技术分析重度寻常痤疮患者和健康人肠道菌群的差异.方法 门诊确诊的重度寻常痤疮患者10例及年龄、性别相匹配的健康人10例,分别收集粪便标本,提取细菌DNA,行16S rRNA测序鉴定微生物的种类,并进行菌群差异分析.结果 两组肠道菌群多样性未发现显著差异,仅在肠道菌群的相对丰度上发现个别具有显著差异的菌.两组标本主要由拟杆菌门、厚壁菌门、变形菌门、放线菌门组成.比较两组在门、属水平上菌群相对丰度,差异均无统计学意义;在种水平上,Blautia producta、Coprococcus eutactus在两组间差异有统计学意义.结论 重度寻常痤疮患者和健康人相比,菌群多样性指数未见明显差异.但某些细菌菌种存在显著差异.     

肠道菌群与阿尔茨海默病的关系

阿尔茨海默病（AD）是一种以进行性记忆丧失和精神、行为功能障碍为特征的中枢神经系统退行性疾病,它是老年痴呆最常见的类型,其发病机制至今仍未明确。肠道菌群作为共生于胃肠道生态系统的大量微生物,可通过肠道微生物-肠-脑轴这一双向交流信息系统与宿主相互作用。肠道菌群失调与肥胖、2型糖尿病以及AD的发病机制密切相关。本文的目的是总结、讨论目前的研究结果以阐述肠道菌群在AD病情发展中的作用,通过了解AD潜在的发病机制,提出新的治疗方法。     

肠道菌群与精神分裂症

精神分裂症是常见的精神科疾病,临床表现为思维、情感、知觉和行为等多方面障碍,常于青壮年起病,病程迁延。据世界卫生组织估计,全球精神分裂症的终生患病率为3．8‰～8．4‰,我国1998年发表的七省流调数据显示,该病在我国的终生患病率为6．55‰。目前精神分裂症的发病机制仍未阐明,临床治疗以对症药物治疗为主。目前关于精神分裂症发病的假说包括遗传、神经递质、神经发育假说等,近期关于精神分裂症发病、神经发育以及炎性免疫方面的关联研究增多,很多研究认为,肠道菌群能够调节人体的免疫炎性反应并影响神经发育,肠道菌群与精神分裂症的关联成为近期的研究热点。人的胃肠道内寄居着种类繁多的微生物,这些微生物称为肠道菌群。人体肠道内寄生着10万亿个细菌,它们能影响体质量和消化能力,抵御感染和自体免疫疾病的患病风险。肠道菌群按一定比例组合,各菌群间互相制约、互相依存,在质和量上形成一种生态平衡。肠道菌群通过各种激素对宿主所消耗的营养物质做出反应,也对宿主产生影响。它们还能产生对体内系统发出信号的化合物,包括神经递质（如γ－氨基丁酸）、氨基酸（如酪氨酸和色氨酸,色氨酸可以被转换成多巴胺和5－羟色胺）等,这些神经递质对人的精神活动会产生不同的影响,包括促进精神分裂症的发生,当肠道菌群间的平衡被破坏,可能通过多种途径引发精神疾病。现就肠道菌群在精神分裂症的发病和治疗中的作用综述如下。     

肠道菌群与脑-肠轴功能相互影响的研究进展

人体肠道内的菌群参与了许多生理功能的维持和疾病的发生。作为大脑和胃肠道功能相互调节的重要桥梁,脑-肠轴功能的正常发挥是肠道菌群维持稳定的条件。脑-肠轴紊乱可激活肠黏膜免疫,对肠道菌群产生影响,使菌群结构发生改变。反之,肠道菌群结构改变亦会影响神经系统发育,导致脑-肠轴功能紊乱,其中迷走神经和血清代谢物质在脑-肠轴功能的调节中发挥重要作用。本文就肠道菌群与脑-肠轴功能相互影响的研究进展作一综述。