Ontogeny of the endocrine cells of the intestine and rectum of sea bass (Dicentrarchus labrax L.): an ultrastructural study

Several endocrine cell types were ultrastructurally characterized during the differentiation of the intestine and rectum of sea bass (Dicentrarchus labrax L.) larvae. Only one cell type (type I) was found in the posterior region of the undifferentiated gut of 5-day-old larvae (phase I). Types V and VI were found in both the intestine and rectum, types II, III and IV in the intestine, and types VII and VIII in the rectum of 9- and 12-day-old larvae (phase II), the rectum alone showing signs of functional differentiation. In phase III larvae, in which both the intestine and rectum were differentiated, types IX, X, XI, XII, XIII, XIV and XV were found in the intestine, only types X, XI and XII being seen in the rectum. Besides these, a new cell type, XVI, was observed in the intestine of 55- and 60-day-old larvae (phase IV), in which the digestive tract was completely differentiated. The endocrine cells appearing in phases I and II showed very scarce secretory granules and the ultrastructural features of undifferentiated cells. Some endocrine cell types in the earliest developmental stages were related to some of those found later. A maturational process of the endocrine cell types paralleled the differentiation of the intestine and rectum, with an apparent increase in the number of secretory granules accompanying organelle development.     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Progress, problems, and perspectives in diagnosis and treatment of Whipple's disease

Whipple's disease is a rare chronic infectious disorder first described in 1907 by G.H. Whipple. The disorder is caused by the newly identified bacterium Tropheryma whipplei and there is evidence that altered immune functions play a role in the manifestation of the disease. The organ systems mostly affected are the joints and the gut, and in the further course often also the heart, lung, brain, and eyes. The intestinal involvement occurs with abdominal pain and diarrhea, which leads to weight loss, malnutrition, and anemia. In some cases the infection spreads to the central nervous system, which may lead to loss of memory, confusion, or disturbances in gait. In the last few years, several steps towards an improved diagnosis of the disease and characterization of the causative bacterium have been made. While untreated disease may be lethal, treatment is often able to eradicate the organism. At present, therapy is based on observations in small patient groups and personal experience. There are different antibiotic therapy regimens often starting with intravenous application for 2 weeks followed by oral medication for 1 year. The first clinical therapy study is ongoing.     

毒死蜱对小鼠焦虑样行为以及肠道菌群的影响

目的 观察毒死蜱暴露致小鼠焦虑样行为及肠道菌群的影响,并探讨两者之间的关系。方法 30只8周龄雄性C57BL/6J小鼠,随机分为3组:对照组(CTL)、毒死蜱低剂量组(CPF2.5)和毒死蜱高剂量组(CPF5),分别灌胃植物油、毒死蜱2.5 mg/kg bw和毒死蜱5 mg/kg bw,1次/d,连续14 d。采用旷场实验(OFT)和高架十字迷宫实验(EPM)对小鼠焦虑样行为进行检测; 采用16S rDNA测序检测粪便肠道菌群变化; 用LEfSe筛选各组间差异菌群; 采用Spearman分析研究肠道差异菌和焦虑样行为指标之间的相关性。结果 与CTL相比,CPF2.5和CPF5小鼠进入旷场中心次数减少(F=6.404,P=0.042,P=0.002),在开臂的活动路程百分比、开臂停留时间百分比以及进入开臂次数百分比均降低(F=8.525,P=0.002,P=0.002; F=17.486,P<0.001, P<0.001; F=4.751,P=0.023,P=0.010),以上差异均有统计学意义。LEfSe 多级物种差异判别分析结果显示,Dubosiella、Muribaculum、Akkermansia等菌在对照组富集; Odoribacter、PrevotellaceaeUCG_001菌在CPF2.5组富集; Proteobacteria、Rhizobiaceae、Ochrobactrum、Rhizobiales菌在CPF5组富集。Spearman相关分析结果表明,Muribaculum与EPM开臂活动路程百分比和开臂停留时间百分比呈正相关(r=0.506, P=0.012; r=0.455, P=0.025),Odoribacter和EPM开臂停留时间百分比呈负相关(r=-0.486, P=0.016)。结论 毒死蜱暴露后引起的小鼠焦虑样行为改变可能与特定的肠道菌群丰度(Muribaculum和Odoribacter)改变相关。     

慢溃宁方对DSS诱导溃疡性结肠炎小鼠NLRP3/Caspase-1/GSDMD细胞焦亡通路和肠道菌群的影响

目的 探讨慢溃宁方对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）小鼠肠道菌群的调控作用,和对NOD样受体（NLR）P3/胱天蛋白酶（Caspase）-1/Gasdermin D（GSDMD）细胞焦亡通路所介导炎症的影响。方法 SPF级C57BL/6小鼠60只,随机分为空白组、模型组、慢溃宁方组（20 g·kg^-1）、美沙拉秦组（0.266 g·kg^-1）,各组15只。小鼠通过自由饮用3%DSS溶液,7 d构建UC模型。造模开始12 h后,治疗组每天灌胃给药,其余组灌胃等体积生理盐水。记录小鼠每日体质量等情况,并评估计算疾病活动指数（DAI）。第8天麻醉后,脱臼颈椎处死小鼠,收集结肠和粪便,记量结肠长度;观察结肠组织苏木素-伊红（HE）染色后的病理学改变;结肠中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）水平用酶联免疫吸附测定法（ELISA）检测;基于16S rRNA测序技术检测各组小鼠粪便中肠道菌群的差异;NLRP3/Caspase-1/GSDMD蛋白结肠组织中含量用蛋白免疫印迹法（Western blot）检测。结果 相较于空白组,模型组小鼠的DAI升高（P<0.01）,结肠长度显著缩短（P<0.01）,结肠黏膜损伤严重,TNFα、IL-1β、IL-18水平均明显升高（P<0.01）,且结肠组织中NLRP3/Caspase-1/GSDMD蛋白含量显著升高（P<0.01）,肠道菌群结构改变,门水平上的放线菌门、拟杆菌门与变形菌门丰度减少,厚壁菌门丰度增加;属水平上的乳酸杆菌、普雷沃氏菌和鼠杆菌属丰度减少,拟杆菌属、芽孢杆菌、毛螺旋菌属NK4A136丰度增加。慢溃宁方组、美沙拉秦组相较于模型组,第3天后DAI显著降低（P<0.01）,结肠长度均显著增加（P<0.01）,结肠的炎症浸润及黏膜结构损伤减轻,且结肠TNF-α、IL-1β、IL-18水平均显著下降（P<0.01）,NLRP3/Caspase-1/GSDMD蛋白在结肠组织中的含量明显降低（P<0.05,P<0.01）,门水平上的变形菌门和拟杆菌门丰度增加,厚壁菌门丰度减少。结论 慢溃宁方可通过抑制细胞经典焦亡通路,缓解UC小鼠结肠炎症反应,减轻结肠损伤,并对肠道菌群紊乱有改善作用。     

The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?

For years, it has been reported that Alzheimer’s disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to the early onset of AD. This review highlights a contribution of the disturbances in the microbiota–gut–brain (MGB) axis to the development of AD. Alteration in the gut microbiota composition is determined by increase in the permeability of the gut barrier and immune cell activation, leading to impairment in the blood–brain barrier function that promotes neuroinflammation, neuronal loss, neural injury, and ultimately AD. Numerous studies have shown that the gut microbiota plays a crucial role in brain function and changes in the behavior of individuals and the formation of bacterial amyloids. Lipopolysaccharides and bacterial amyloids synthesized by the gut microbiota can trigger the immune cells residing in the brain and can activate the immune response leading to neuroinflammation. Growing experimental and clinical data indicate the prominent role of gut dysbiosis and microbiota–host interactions in AD. Modulation of the gut microbiota with antibiotics or probiotic supplementation may create new preventive and therapeutic options in AD. Accumulating evidences affirm that research on MGB involvement in AD is necessary for new treatment targets and therapies for AD.     

Microbiome as Mediator of Diet on Colorectal Cancer Risk: The Role of Vitamin D,Markers of Inflammation and Adipokines

Obesity and diet are associated with colorectal cancer (CRC) risk, and microbiome could mediate this risk factor. To investigate this interaction, we performed a case–control study (34 CRC cases and 32 controls) and analyzed fecal microbiota composition using 16S rRNA metabarcoding and sub-sequential shotgun analyses of genomic bacterial DNA to evaluate the role of microbiome and diet in CRC etiology, taking into account vitamin D and other risk biomarkers. Dietary habits were evaluated using a short questionnaire. Multivariate methods for data integration and mediation analysis models were used to investigate causal relationships. CRC cases were significantly more often deficient in vitamin D than controls (p = 0.04); FokI and CYP24A1 polymorphism frequency were different between cases and controls (p = 0.03 and p = 0.02, respectively). A diet poor in fatty fish and rich in carbohydrates was found to be significantly associated with CRC risk (p = 0.011). The mediation analysis confirmed the significant role of the microbiome in mediating CRC risk—increasing levels of Bifidobacteria/Escherichia genera ratio, an indicator of “healthy” intestinal microbiome, can overcome the effect of diet on CRC risk (p = 0.03). This study suggests that microbiome mediates the diet effect on CRC risk, and that vitamin D, markers of inflammation, and adipokines are other factors to consider in order to achieve a better knowledge of the whole carcinogenic process.     

Magnesium in Obesity,Metabolic Syndrome,and Type 2 Diabetes

Magnesium (Mg²⁺) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg²⁺ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg²⁺ deficiency, such as the lack of a clear definition of Mg²⁺ nutritional status, the use of different Mg²⁺ salts and dosage and the different duration of the Mg²⁺ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg²⁺, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.     

Effects of a Rice Bran Dietary Intervention on the Composition of the Intestinal Microbiota of Adults with a High Risk of Colorectal Cancer: A Pilot Randomised-Controlled Trial

Rice bran exhibits chemopreventive properties that may help to prevent colorectal cancer (CRC), and a short-term rice bran dietary intervention may promote intestinal health via modification of the intestinal microbiota. We conducted a pilot, double-blind, randomised placebo-controlled trial to assess the feasibility of implementing a long-term (24-week) rice bran dietary intervention in Chinese subjects with a high risk of CRC, and to examine its effects on the composition of their intestinal microbiota. Forty subjects were randomised into the intervention group (n = 19) or the control group (n = 20). The intervention participants consumed 30 g of rice bran over 24-h intervals for 24 weeks, whilst the control participants consumed 30 g of rice powder on the same schedule. High rates of retention (97.5%) and compliance (≥91.3%) were observed. No adverse effects were reported. The intervention significantly enhanced the intestinal abundance of Firmicutes and Lactobacillus, and tended to increase the Firmicutes/Bacteroidetes ratio and the intestinal abundance of Prevotella_9 and the health-promoting Lactobacillales and Bifidobacteria, but had no effect on bacterial diversity. Overall, a 24-week rice bran dietary intervention was feasible, and may increase intestinal health by inducing health-promoting modification of the intestinal microbiota. Further larger-scale studies involving a longer intervention duration and multiple follow-up outcome assessments are recommended.