Intentionally induced intestinal barrier dysfunction causes inflammation,affects metabolism,and reduces productivity in lactating Holstein cows

Study objectives were to evaluate the effects of intentionally reduced intestinal barrier function on productivity, metabolism, and inflammatory indices in otherwise healthy dairy cows. Fourteen lactating Holstein cows (parity 2.6 ± 0.3; 117 ± 18 d in milk) were enrolled in 2 experimental periods. Period 1 (5 d) served as the baseline for period 2 (7 d), during which cows received 1 of 2 i.v. treatments twice per day: sterile saline or a gamma-secretase inhibitor (GSI; 1.5 mg/kg of body weight). Gamma-secretase inhibitors reduce intestinal barrier function by inhibiting crypt cell differentiation into absorptive enterocytes. During period 2, control cows receiving sterile saline were pair-fed (PF) to the GSI-treated cows, and all cows were killed at the end of period 2. Administering GSI increased goblet cell area 218, 70, and 28% in jejunum, ileum, and colon, respectively. In the jejunum, GSI-treated cows had increased crypt depth and reduced villus height, villus height-to-crypt depth ratio, cell proliferation, and mucosal surface area. Plasma lipopolysaccharide binding protein increased with time, and tended to be increased 42% in GSI-treated cows relative to PF controls on d 5 to 7. Circulating haptoglobin and serum amyloid A concentrations increased (585- and 4.4-fold, respectively) similarly in both treatments. Administering GSI progressively reduced dry matter intake (66%) and, by design, the pattern and magnitude of decreased nutrient intake was similar in PF controls. A similar progressive decrease (42%) in milk yield occurred in both treatments, but we observed no treatment effects on milk components. Cows treated with GSI tended to have increased plasma insulin (68%) and decreased circulating nonesterified fatty acids (29%) compared with PF cows. For both treatments, plasma glucose decreased with time while β-hydroxybutyrate progressively increased. Liver triglycerides increased 221% from period 1 to sacrifice in both treatments. No differences were detected in liver weight, liver moisture, or body weight change. Intentionally compromising intestinal barrier function caused inflammation, altered metabolism, and markedly reduced feed intake and milk yield. Further, we demonstrated that progressive feed reduction appeared to cause leaky gut and inflammation.     

Maternal rumen and milk microbiota shape the establishment of early-life rumen microbiota in grazing yak calves

Early-life gut microbial colonization and development exert a profound impact on the health and metabolism of the host throughout the life span. The transmission of microbes from the mother to the offspring affects the succession and establishment of the early-life rumen microbiome in newborns, but the contributions of different maternal sites to the rumen microbial establishment remain unclear. In the present study, samples from different dam sites (namely, oral, rumen fluid, milk, and teat skin) and rumen fluid of yak calves were collected at 6 time points between d 7 and 180 postpartum to determine the contributions of the different maternal sites to the establishment of the bacterial and archaeal communities in the rumen during early life. Our analysis demonstrated that the dam's microbial communities clustered according to the sites, and the calves' rumen microbiota resembled that of the dam consistently regardless of fluctuations at d 7 and 14. The dam's rumen microbiota was the major source of the calves' rumen bacteria (7.9%) and archaea (49.7%) compared with the other sites, whereas the potential sources of the calf rumen microbiota from other sites varied according to the age. The contribution of dam's rumen bacteria increased with age from 0.36% at d 7 to 14.8% at d 180, whereas the contribution of the milk microbiota showed the opposite trend, with its contribution reduced from 2.7% at d 7 to 0.2% at d 180. Maternal oral archaea were the main sources of the calves' rumen archaea at d 14 (50.4%), but maternal rumen archaea became the main source gradually and reached 66.2% at d 180. These findings demonstrated the potential microbial transfer from the dam to the offspring that could influence the rumen microbiota colonization and establishment in yak calves raised under grazing regimens, providing the basis for future microbiota manipulation strategies during their early life.     

Molecular Pathogenesis of NASH

Nonalcoholic steatohepatitis (NASH) is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression.     

The Metabolic Role of Gut Microbiota in the Development of Nonalcoholic Fatty Liver Disease and Cardiovascular Disease

The prevalence of metabolic disorders, such as type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease (NAFLD), which are common risk factors for cardiovascular disease (CVD), has dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.     

母乳低聚糖对Caco-2肠上皮细胞屏障功能的影响

母乳低聚糖(HMOs)是母乳中的关键活性成分,具有调节肠道菌群,保护肠道屏障完整性和调节免疫等重要的生理功能。本研究构建Caco-2细胞肠上皮屏障及炎症损伤模型,用2’-岩藻糖基乳糖(2’-FL)、3’-唾液酸乳糖(3’-SL)和乳糖-N-新四糖(LNnT)3种分别代表中性岩藻糖基化、唾液酸化和中性非岩藻糖基化的HMO进行干预。通过测定细胞跨膜电阻值表征肠屏障完整性,采用酶联免疫吸附法测定炎症因子的分泌水平,以及实时荧光定量PCR技术分析紧密连接和炎症相关基因的表达水平,旨在探究HMO对肠屏障功能的保护作用及其调控机制。结果表明,与阴性对照组相比,3种HMO均能浓度依赖性地提高跨膜电阻值,降低IL-6和IL-8的基因表达水平和分泌量,其中10 mg/mL的3’-SL干预可使其降低至空白组水平;抑制IL-1β、TNF-α、COX-2和iNOS的基因表达,其中10 mg/mL的HMO干预组基因表达水平最低。在高质量浓度的HMO干预下Claudin-1、Claudin-3、ZO-1、ZO-2和Occludin的基因表达水平上调4倍,并抑制NF-κB信号通路的激活但该作用未表现出浓度依赖性。3种HMO在高质量浓度下(2.4 mg/mL和10 mg/mL)能发挥显著的肠屏障保护作用和抗炎活性,研究结果为HMO增强肠屏障功能和免疫调节功能的应用提供科学证据。     

食用菌多糖调节炎症性肠病研究进展

文章从食用菌多糖的组成结构、生理功效,食用菌多糖对炎症性肠病的直接干预以及通过调控肠道菌群间接干预炎症性肠病等方面进行了综述,并对食用菌多糖的深入研究提出了建议。     

微生态制剂调节便秘、腹泻人群肠道菌群结构与产短链脂肪酸关键菌属的相关性

为探究微生态制剂对健康、便秘和腹泻人群肠道菌群结构的调节能力。本研究以健康、便秘和腹泻人群 为对象,令其定时、定量摄入水苏糖（stachyose tetrahydrate,Sta）、益生菌纯粉（probiotics power,PP）、益生 菌剂（probotic preparations,PPrs）3 种微生态制剂,共6 周,采集新鲜粪便样本并提取DNA,利用Ion torrent PGM 二代测序技术进行16S rRNA V3区扩增子测序,并用气相色谱检测粪便中的短链脂肪酸（short-chain fatty acids, SCFAs）表达水平,最后联合多变量统计学分析方法对测序数据进行多样性分析。结果表明：绝大多数序列属 于硬壁菌门（Firmicutes）和拟杆菌门（Bacteroidetes）,约占总序列数的94.37%。随着微生态制剂的摄入,受 试人群肠道菌群的群落结构多样性明显增加,毛螺菌科（Lachnospiraceae）中的Blautia、Lachnospira以及瘤胃菌 科（Ruminococcaceae）中的Faecalibacterium、Oscillospir等与产SCFAs相关的菌属都明显地增长,其中Blautia和 Faecalibacterium与SCFAs含量呈显著正相关。SCFAs的含量以及肠道中相应菌群的增长与减少都与微生态制剂的成 分相关,在3 组受试人群中,服用Sta组,丙酸含量显著增加,乙酸与丁酸含量也在2 周左右有所增加,并伴随产 SCFAs的菌属快速且大量增长;PP组肠道中只有乙酸含量有所增加,丙酸和丁酸含量呈现降低的趋势,而产SCFAs 的菌属增长较明显;服用PPrs组,乙酸和丁酸含量明显增加,且便秘和腹泻人群在停止服用后,其SCFAs的含量 接近于健康人群,常见的Bifidobacterium、Lactobacillus、Parabacteroides等外源性益生菌均明显增长,可能性致病 菌相对丰度降低,表明服用PPrs对肠道菌群结构的调节作用以及影响更大。此外,根据肠型的分析,Bacteroides和 Prevotella在饮食的共同驱动下会调整并改变肠型,而仅通过所选择的微生态制剂的作用,在驱动肠型改变方面不 显著。综上所述,肠道疾病状态的人群服用微生态制剂后,肠道菌群结构向正常人群的状态调整,菌群多样性和 SCFAs表达水平提高,表现出持续抑制肠道有害细菌生长,促进有益菌的增殖,以此来维持肠道菌群结构的稳态。 经扩增子测序分析获得初步结论为：微生态制剂有改变腹泻、便秘人群肠道菌群整体结构的功效,并且PPrs要比单 一的Sta或PP调整肠道菌群的能力更突出。     

益生菌缓解肥胖形成相关机制及研究进展

肥胖及相关代谢综合征已成为世界范围内的公共健康问题。研究表明,肠道菌群与肥胖的形成密切相关,肠道菌群失调导致脂代谢紊乱、肠道通透性及氧化应激等改变。益生菌(主要包括乳酸菌和双歧杆菌)是一类能对宿主生理功能产生有益作用的微生物,能在肠道中存活并定殖,改善肠道菌群紊乱,进一步缓解肥胖的形成。本文主要围绕益生菌对肥胖的干预作用及相关机制进行综述,以为肥胖相关的研究提供参考。     

魔芋粉对小鼠急性酒精性胃黏膜损伤和慢性酒精性肠损伤的影响

目的：研究魔芋粉对小鼠急性酒精性胃黏膜损伤和慢性酒精性肠损伤的影响,为开发天然的预防酒精性 脏器损伤的食品提供理论依据。方法：用乙醇体积分数56%的白酒灌胃造成急性酒精性胃黏膜损伤和慢性酒精性 肠损伤模型,并用不同剂量的魔芋粉（170、240、400 mg/kg mb·d）灌胃干预,设正常组和模型组。检测指标包 括胃黏膜溃疡指数、胃组织中超氧化物歧化酶（superoxide dismutase,SOD）活力和丙二醛（methane dicarboxylic aldehyde,MDA）、一氧化氮（nitric monoxide,NO）、前列腺素E2（prostaglandin E2,PGE2）的含量,盲肠内容 物中游离氨、短链脂肪酸（short-chain fatty acids,SCFA）、肠道微生物的含量,并观察胃、肠组织病理学切片。 结果：与模型组比较,魔芋粉中、高剂量组小鼠胃溃疡指数分别降低了25.42%和28.18%;MDA含量分别下降了 38.07%和47.32%;SOD活力和NO、PGE2、双歧杆菌、乳杆菌含量明显升高;盲肠的游离氨含量、肠球菌数量明显 降低,乙酸、正丁酸、戊酸含量升高,胃黏膜和肠道组织得到明显改善。结论：魔芋粉对小鼠急性酒精性胃黏膜损 伤与慢性酒精性肠损伤具有保护作用,其影响作用可能是通过降低胃黏膜脂质过氧化物产物含量,增强胃黏膜抗氧 化能力,改善肠道微生态,增强胃黏膜和肠道组织的屏障作用从而实现对慢性酒精性肠损伤的保护。     

黄精提取物的体外模拟消化特性及对肠道菌群的影响

目的：采用体外模拟消化结合16S rDNA高通量测序技术探究黄精提取物活性成分含量的变化及对肠道菌群调节作用。方法：通过加热回流法制备黄精提取物,测定体外模拟消化前后黄精提取物中多糖、皂苷和黄酮的含量,并考察其对α-葡萄糖苷酶的抑制能力。基于16S rDNA高通量测序分析黄精提取物对肠道菌群的影响。结果：黄精提取物含有多糖、皂苷、黄酮的含量分别为0.4732、0.0632和0.0754 mg/mL。经体外模拟消化后,多糖、皂苷、黄酮的含量均显著降低（P<0.05）,且加入消化酶组显著低于未加入消化酶组（P<0.05）。另外,消化后黄精提取物对α-葡萄糖苷酶抑制能力显著降低（P<0.05）。随着体外发酵时间的增加,黄精提取物处理组粪便发酵的pH从初始的6.85下降到4.13,48 h后发酵液呈弱酸性。肠道菌群分析表明,黄精提取物能改变肠道菌群结构,尤其在门、属水平上具有一定程度的改善作用。黄精提取物可增加厚壁菌门（Firmicutes）丰度,降低变形菌门（Proteobacteria）的丰度,增加双歧杆菌属（Bifidobacterium）相对丰度,并且显著降低纺锤链杆菌属（Fusicatenibacter）相对丰度（P<0.05）。结论：黄精提取物经体外模拟消化后多糖、皂苷和黄酮的含量显著降低（P<0.05）,对α-葡萄糖苷酶的抑制作用降低,可改变肠道微生物群落结构,对肠道菌群具有一定的调节作用。本研究可为黄精精深加工及调节肠道菌群方面提供理论参考。