Polydatin alleviates bleomycin-induced pulmonary fibrosis and alters the gut microbiota in a mouse model

To investigate the effect and mechanism of polydatin on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The contents of TNF-α, LPS, IL-6 and IL-1β in lung tissue, intestine and serum were detected by ELISA. Gut microbiota diversity was detected by 16S rDNA sequencing; R language was used to analyse species composition, α-diversity, β-diversity, species differences and marker species. Mice were fed drinking water mixed with four antibiotics (ampicillin, neomycin, metronidazole, vancomycin; antibiotics, ABx) to build a mouse model of ABx-induced bacterial depletion; and faecal microbiota from different groups were transplanted into BLM-treated or untreated ABx mice. The histopathological changes and collagen I and α-SMA expression were determined. Polydatin effectively reduced the degree of fibrosis in a BLM-induced pulmonary fibrosis mouse model; BLM and/or polydatin affected the abundance of the dominant gut microbiota in mice. Moreover, faecal microbiota transplantation (FMT) from polydatin-treated BLM mice effectively alleviated lung fibrosis in BLM-treated ABx mice compared with FMT from BLM mice. Polydatin can reduce fibrosis and inflammation in a BLM-induced mouse pulmonary fibrosis model. The alteration of gut microbiota by polydatin may be involved in the therapeutic effect.     

蜜蜂肠道菌群结构功能研究进展

在长期的共同进化中,肠道菌群与其宿主形成了紧密的联系,为宿主提供了许多有益的作用。作为一种社会性昆虫,蜜蜂的生活习性为其肠道菌群提供了良好而稳定的传播途径,因此,蜜蜂与其肠道菌群形成了一种紧密的互惠互利共生关系。近年来,随着对蜜蜂肠道菌群了解的不断加深,对蜜蜂肠道菌群功能的研究也不断深入,大量研究表明蜜蜂的肠道菌群在宿主食物的消化代谢、宿主免疫的激活和抵抗致病菌、调节宿主生理等方面都有着重要的作用,同时破坏肠道菌群的稳定对蜜蜂的健康有着明显的负面影响。本文对近年来西方蜜蜂肠道菌群功能研究进行了总结,旨在为进一步深入探索蜜蜂肠道菌群与其宿主的相互作用及在养蜂生产上应用肠道菌群防控疾病提供参考。     

桃红四物汤对缺糖缺氧大鼠脑微血管内皮细胞VEGF、VEGFR-2、Akt基因及蛋白表达的作用机制研究

摘要 目的：探讨桃红四物汤对缺糖缺氧（OGD）大鼠脑微血管内皮细胞（rBMECs）血管内皮生长因子（VEGF）、血管内皮生长因子受体2（VEGFR-2）、蛋白激酶B（Akt）基因及蛋白表达的影响及其作用机制。方法：取rBMECs进行培养并随机分为正常组培养、模型组培养、桃红四物汤（0.4 mg/mL）组和桃红四物汤（0.8 mg/mL）组,除正常组外,其余三组采用氧糖剥夺实验构建OGD损伤模型。桃红四物汤组在造模前1 h按0.4 mg/mL、0.8 mg/mL浓度加入桃红四物汤,而正常组及模型组则加入等量体积生理盐水。实时定量聚合酶链反应（qRT-PCR）、蛋白免疫印迹试验检测VEGF、VEGFR-2、Akt基因及蛋白表达情况。结果：与正常组比较,模型组细胞凋亡率显著升高（P＜0.05）。与模型组比较,桃红四物汤（0.4 mg/mL）组和桃红四物汤（0.8 mg/mL）组均降低,且以桃红四物汤（0.8 mg/mL）组最为显著（P＜0.05）。与正常组比较,模型组rBMECs中Akt、VEGFR-2、VEGF相对mRNA和蛋白表达水平显著升高（P＜0.05）。与模型组比较,桃红四物汤（0.4 mg/mL）组和桃红四物汤（0.8 mg/mL）组显著降低,且以桃红四物汤（0.8 mg/mL）组最为显著（P＜0.05）。结论：桃红四物汤可能通过降低OGD条件下rBMECs中VEGF、VEGFR-2、Akt基因及蛋白表达水平,从而发挥抑制内皮细胞的凋亡,保持内皮细胞的完整性,这可能是桃红四物汤对脑保护的机制之一。     

基于PI3K/Akt信号通路探讨桃红四物汤促进老年股骨粗隆间骨折患者PFNA术后骨折愈合的疗效及其机制

摘要 目的：基于磷酯酰肌醇3激酶（PI3K）/丝氨酸蛋白激酶（Akt）信号通路探讨桃红四物汤促进老年股骨粗隆间骨折患者股骨近端抗旋髓内钉（PFNA）术后骨折愈合的疗效及其机制。方法：选取2021年7月-2022年12月期间遂宁市中医院收治的90例老年股骨粗隆间骨折行PFNA术患者,按照随机数字表法将患者分为对照组和研究组,各为45例。对照组术后接受常规干预,研究组在对照组基础上接受桃红四物汤干预。对比两组中医证候积分、骨折愈合时间、Harris髋关节功能评分、血液流变学、PI3K/Akt信号通路相关指标。结果：治疗后研究组髋部疼痛、痛有定处、神疲乏力、患肢软而无力、头晕眼花、失眠健忘、自汗畏风寒、胸闷气短、肌肤甲错、面色晄白无华评分和总分低于对照组（P<0.05）。研究组的骨折愈合时间短于对照组,Harris髋关节功能评分高于对照组（P<0.05）。研究组的红细胞压积、血浆比黏度、全血比黏度、红细胞电泳时间低于对照组（P<0.05）。研究组治疗后PI3K mRNA、AktmRNA高于对照组（P<0.05）。结论：老年股骨粗隆间骨折患者PFNA术后使用桃红四物汤,可促进患者临床预后转归,降低中医证候积分,促进髋关节功能恢复,缩短骨折愈合时间,改善机体血液流变学,调节PI3K/Akt信号通路表达。     

The role of intestinal stem cell within gut homeostasis: Focusing on its interplay with gut microbiota and the regulating pathways

Intestinal stem cells (ISCs) play an important role in maintaining intestinal homeostasis via promoting a healthy gut barrier. Within the stem cell niche, gut microbiota linking the crosstalk of dietary influence and host response has been identified as a key regulator of ISCs. Emerging insights from recent research reveal that ISC and gut microbiota interplay regulates epithelial self-renewal. This article reviews the recent knowledge on the key role of ISC in their local environment (stem cell niche) associating with gut microbiota and their metabolites as well as the signaling pathways. The current progress of intestinal organoid culture is further summarized. Subsequently, the key challenges and future directions are discussed.     

Effects of therapeutic hypothermia on the gut microbiota and metabolome of infants suffering hypoxic-ischemic encephalopathy at birth

Neonatal hypoxic ischemic encephalopathy (HIE) in the perinatal period can lead to significant neurological deficits in later life. Total body cooling (TBC) is a neuroprotective strategy used in the treatment of HIE and has been shown to reduce seizures and improve neurodevelopmental outcomes in treated infants. Little is known, however, about the effects of HIE/TBC on the developing gut microbiota composition and subsequent metabolic profile. Ten term infants with HIE who received TBC at 33.5 °C for 72 h were recruited. A control group consisted of nine healthy full term infants. Faecal samples were collected from both groups at 2 years of age and stored at −20 °C. 16S rRNA amplicon Illumina sequencing was carried out to determine gut microbiota composition and 1H NMR analysis was performed to determine the metabolic profile of faecal water. The gut microbiota composition of the HIE/TBC infants were found to have significantly lower proportions of Bacteroides compared to the non-cooled healthy control group. Alpha diversity measures detected significantly lower diversity in microbial richness in the HIE/TBC infant group compared to the control infants (Shannon index, <0.05). High inter-individual variation was found in gut microbiota composition and metabolic profile of both groups. Initial principal coordinate analysis and hierarchal clustering of compounds on MetaboAnalyst 3.0 indicated no clear separation in the metabolic profile of these two infant groups. These results suggest that there is no significant impact on the gut microbial development of HIE/TBC infants compared to healthy infants at 2 years of life. To our knowledge this is the first study to report the gut microbiota composition and metabolic profile of infants who have experienced HIE/TBC at birth.     

Val-Val-Tyr-Pro protects against non-alcoholic steatohepatitis in mice by modulating the gut microbiota and gut-liver axis activation

Val-Val-Tyr-Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride-induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non-alcoholic steatohepatitis (NASH) have not been discovered. Our present study was designed to investigate the preventive effect of VVYP on NASH and its underlying specific mechanisms. We found that VVYP inhibited the cytotoxicity and lipid accumulation in L-02 cells that were exposed to a mixture of free fatty acid (FFA). VVYP effectively alleviated the liver injury induced by methionine-choline-deficient (MCD) diet, demonstrated by reducing the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/triglycerides (TG)/non-esterified fatty acids (NEFA) and improving liver histology. VVYP decreased expression levels of lipid synthesis-related genes and reduced levels of the proinflammation cytokines in the liver of mice fed by MCD diet. Moreover, VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction induced by MCD diet. Meanwhile, VVYP significantly increased the abundance of beneficial bacteria such as Eubacteriaceae, coriobacteriacease, Desulfovibrionaceae, S24-7 and Bacteroidia in high-fat diet (HFD)-fed mice, however, VVYP reduced the abundance of Lactobacillus. Moreover, VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)-associated genes and inhibited subsequent liver inflammatory responses. These results indicated that the protective role of VVYP on NASH is mediated by modulating gut microbiota imbalance and related gut-liver axis activation. VVYP might be a promising drug candidate for NASH.     

A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice

Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community–host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to ‘fingerprint'' microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography–mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota''s metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest ‘personalized'' aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host.     

肺部菌群和肠道菌群及其互作与肺癌发生发展的相关性研究进展

肺部菌群及肠道菌群与肺癌密切相关,研究发现与健康人群相比肺癌患者的肺部及肠道菌群发生失调,即菌群组成结构发生显著改变。随着“肠-肺轴”概念的提出,肺部及肠道菌群在人体内的紧密联系越发受到重视,因此关于肺部及肠道菌群的研究对于阐明肺癌的发生发展机制有重要的指引作用。文中综述了肺癌患者肺部及肠道菌群的组成特点及可能的互作机制,强调了肠-肺轴中免疫系统的重要性,最后总结了肺部及肠道菌群对肺癌临床治疗的影响,并对肺部及肠道菌群可作为肺癌早期诊断与治疗的新颖靶点进行了展望。     

Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility

Organ–organ crosstalk is involved in homeostasis. Gastrointestinal symptoms are common in patients with renal failure. The aim of this study was to elucidate the relationship between gastrointestinal motility and gastrointestinal symptoms in chronic kidney disease. We performed studies in C57BL/6 mice with chronic kidney disease after 5/6 nephrectomy. Gastrointestinal motility was evaluated by assessing the ex vivo responses of ileum and distal colon strips to electrical field stimulation. Feces were collected from mice, and the composition of the gut microbiota was analyzed using 16S ribosomal RNA sequencing. Mice with chronic kidney disease after 5/6 nephrectomy showed a decreased amount of stool, and this constipation was correlated with a suppressed contraction response in ileum motility and decreased relaxation response in distal colon motility. Spermine, one of the uremic toxins, inhibited the contraction response in ileum motility, but four types of uremic toxins showed no effect on the relaxation response in distal colon motility. The 5/6 nephrectomy procedure disturbed the balance of the gut microbiota in the mice. The motility dysregulation and constipation were resolved by antibiotic treatments. The expression levels of interleukin 6, tumor necrosis factor-α, and iNOS in 5/6 nephrectomy mice were increased in the distal colon but not in the ileum. In addition, macrophage infiltration in 5/6 nephrectomy mice was increased in the distal colon but not in the ileum. We found that 5/6 nephrectomy altered gastrointestinal motility and caused constipation by changing the gut microbiota and causing colonic inflammation. These findings indicate that renal failure was remarkably associated with gastrointestinal dysregulation.     

持续低氧条件下大鼠肠道微生物变化及其与心肌损伤的关联研究

【目的】研究持续性常压低氧对大鼠肠道微生物的影响,并分析其与低氧性心肌肥厚的关联性。【方法】雌性无特异性病原体(specific-pathogen-free, SPF)级SD (Sprague-Dawley)大鼠,按随机数字表法分为2组：常氧组和低氧组。实验开始后,低氧组大鼠置于低氧舱中,氧气浓度设定为10%,持续暴露30 d,常氧组大鼠正常条件饲养。每天记录大鼠体重,并于低氧前(0 d)和低氧后(30 d)分别收集粪便进行16S rRNA基因扩增子测序,测定肠道微生物组的变化。实验结束后进行血常规、血生化和器官指数分析;采用实时定量聚合酶链式反应(quantitativereal-time polymerasechainreaction,qRT-PCR)检测右心室组织中4种分子标志物心房利钠肽基因(atrial natriureticpeptide,ANP)、脑钠肽基因(brainnatriureticpeptide,BNP)、心肌肌球蛋白重链6基因(myosin heavy chain 6, Myh6)、心肌肌球蛋白重链7基因(myosin heavy chain 7, Myh7)...     

运动调控肠道菌群在阿尔茨海默病防治中的应用

阿尔茨海默病（Alzheimer's disease,AD）是一种起病隐匿且呈进行性发展的中枢神经系统退行性疾病,以记忆障碍、语言功能和其他认知能力衰退为主要症状,可导致患者日常生活能力下降,出现精神行为异常,给家庭和社会带来极大的负担。肠道菌群已被发现不仅是免疫和代谢健康的重要组成部分,而且对胃肠道和中枢神经系统的发育具有重要作用。运动医学作为一种新兴的治疗手段,能显著改善肠道菌群紊乱,调节脾胃功能,改善代谢和睡眠,延缓AD的进程。本文通过总结运动及其相关因素对肠道菌群的影响,探讨AD的预防和控制。

     

大黄酸调节AMPK/mTOR信号通路对急性胰腺炎大鼠肠道菌群失调和肠屏障损伤的影响

探讨大黄酸调节腺苷酸激活蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路对急性胰腺炎（AP）大鼠肠道菌群失调和肠屏障损伤的影响。

SPF级雄性7周龄SD大鼠50只,随机取10只作为假手术组,其余大鼠注射牛磺胆酸钠构建AP大鼠模型,将AP大鼠随机分为模型组、大黄酸组（100 mg/kg）、二甲双胍组（200 mg/kg）、大黄酸+二甲双胍组（100 mg/kg大黄酸+200 mg/kg二甲双胍）,每组10只,每天1次,连续注射2周。模型组和假手术组大鼠给予等量生理盐水。ELISA法检测血清DAO活性、TNF-α和IL-6水平;H&;E染色检测胰腺和结肠组织病理学变化;进行粪便16S rRNA基因测序;Western Blot检测结肠屏障相关蛋白及AMPK-mTOR通路相关蛋白表达。

与假手术组相比,模型组大鼠血清DAO活性、IL-6、TNF-α水平以及胰腺和结肠组织病理损伤评分、AMPK水平、mTOR蛋白水平、埃希菌属相对丰度均显著升高（均P＜0.05）,Shannon指数、Simpson指数、Chao1指数以及乳杆菌、双歧杆菌相对丰度和ZO-1蛋白、Occludin蛋白水平均显著降低（均P＜0.05）;与模型组相比,大黄酸组大鼠血清DAO活性、IL-6、TNF-α水平以及胰腺和结肠组织病理损伤评分、AMPK水平、mTOR蛋白水平、埃希菌属相对丰度均显著降低（均P＜0.05）,Shannon指数、Simpson指数、Chao1指数以及乳杆菌、双歧杆菌相对丰度和ZO-1蛋白、Occludin蛋白水平均显著增加（均P＜0.05）,而二甲双胍组以上指标结果与大黄酸组趋势相反;二甲双胍逆转了大黄酸对AP大鼠肠道菌群失调和肠屏障损伤的治疗效果。

大黄酸可能通过下调AMPK/mTOR信号通路对AP大鼠肠道菌群失调和肠屏障损伤起到改善作用。