宏基因组学在胃肠道微生物研究中的应用

动物胃肠道中普遍存在大量共生微生物群,对于它们的研究一直受制于纯培养技术。随着分子生物学的快速发展及其在微生物学及生态学上的应用,针对未培养微生物研究的一门新型学科——宏基因组技术应运而生并迅速发展。通过提取胃肠道粘膜表面以及内容物中微生物DNA,构建总DNA文库的方法,利用基因组学的研究策略,来研究胃肠道中微生物遗传组成及群落功能。宏基因组技术在胃肠道微生物研究中广泛的应用,对于医学、生态学、生物能源利用等领域的研究具有重大的价值。     

Pharmacological effects of oral saikosaponin a may differ depending on conditions of the gastrointestinal tract

Saikosaponin a and its 8 derivatives, structural isomers and their monoglycosides and aglycones, which were formed in the gastrointestinal tract with their fecal contents depending on food intake, showed different effects on protein synthesis by rat hepatocytes in primary culture. Saikosaponin a and its monoglycoside and aglycone were detectable in plasma of rats when saikosaponin a was orally administered. Pharmacological effects of saikosaponin a when orally administered may differ depending on conditions of the gastrointestinal tract.     

An isolated abdominal preparation in the rat

A methodological approach proposed lies in the use of a complex abdominal preparation (an alimentary complex) of the gastrointestinal tract containing rat stomach, duodenum, small and large intestines and pancreas. The method is based on perfusion of the preparation vessels, namely of the vessels of the gastrointestinal tract or its parts both in situ and isolation of this alimentary complex. The alimentary complex is intended for solution of many problems of normal and pathological physiology, pharmacology and biology, permitting a deeper and broader insight into alimentary, transport, endocrine and regulatory functions of the gastrointestinal tract.     

Effects of anthocyanins and anthocyanin-rich extracts on the risk for cancers of the gastrointestinal tract

Anthocyanins are the largest group of water-soluble pigments in the plant kingdom. Anthocyanins are responsible for most of the red, blue, and purple colors of fruits, vegetables, flowers, and other plant tissues or products. In recent years, numerous studies have shown that anthocyanins display a wide range of biological activities. This review summarises recent literature evidence on the association of anthocyanins and anthocyanin-rich extracts consumption with the risk for gastrointestinal tract cancer, concentrating on the results from in vivo animal model tumor systems, as well as data from human epidemiological studies. Potential cancer chemopreventive activities of anthocyanins were revealed from in vitro studies. In vivo animal model tumor systems showed that dietary anthocyanins inhibit cancers of the gastrointestinal tract. Some epidemiological studies have revealed protective effects of anthocyanins consumption on gastrointestinal cancer risk in humans. Pharmacokinetic data indicate that absorption of anthocyanins into the bloodstream of rodents and humans is minimal, suggesting that they may have little efficacy in tissues other than the gastrointestinal tract and skin. Future studies should be undertaken to determine if the anticancer effects of anthocyanins are due to the parent compounds and/or to their metabolites.     

Interrelationship of the cardiovascular and digestive systems in the genesis of experimental atherosclerosis]

In chronic experiments (up to 2 years) on dogs on atherogenic diets the motor activity of the gastrointestinal tract, cholesterol, the phospholipid level in the blood and in the intestinal secretion as well as the morphology of the small intestine and the vascular system were examined. At the early stages of atherosclerosis (up to 4 months) the rise of the blood cholesterol level was followed by an increase in the periods of the activity of the gastrointestinal tract, a rise of cholesterol discharge by the small intestine, and the development of the hypertrophic process in the mucous membrane. At the later stages a change in the mucous membrane of the small intestine was observed with development of a dystrophic-atrophic process, a disturbance of motor activity of the gastrointestinal tract and of the correlations between the cholesterol content in the blood and its discharge by the small intestine. This period was characterized by a high and persistent hypercholesterolemia and pronounced atherosclerotic changes in the vascular system.     

Gastrointestinal somatostatin: distribution, secretion and physiological significance

Somatostatin-like immunoreactivity (SLI) has been found throughout the gastrointestinal tract in all species examined. In the stomach it is mainly present in endocrine-type D-cells whereas in the intestine there is also an extensive distribution in enteric neurones. In all regions of the gastrointestinal tract multiple forms of somatostatin exist. A precursor (prosomatostatin) has been partially sequenced, three forms with 20 (SS-20), 25 (SS-25) and 28 (SS-28) amino acids completely sequenced, and somatostatin-14 (SS-14) demonstrated by radioimmunoassay. Both SS-14 and SS-28 exert a wide range of actions on the gastrointestinal tract and there is strong supportive evidence for a role in the regulation of gastric acid and gastrin secretion, gastrointestinal motility and intestinal transport. Both in vivo and in vitro studies on the secretion of gastric SLI into the vasculature have shown that nutrients initiate the process but that subsequent events are regulated by a complex interplay between hormonal and neuronal pathways. GIP is one of the most potent hormonal secretagogues. In the stomach, acetylcholine, opioid peptides and substance P are probably involved in parasympathetic inhibitory pathways and gastrin releasing peptide in stimulatory pathways. The sympathetic nerves are also stimulatory. Regulation of secretion of intestinal SLI has not been so extensively studied. Although SLI is also found in the gastrointestinal lumen the significance is unclear. Despite these advances the exact route of delivery of somatostatin to its target organs is uncertain and paracrine, endocrine and neural pathways may all be involved.     

The gastrointestinal microbiome: a malleable, third genome of mammals

The nonpathogenic, mutualistic bacteria of the mammalian gastrointestinal tract provide a number of benefits to the host. Recent reports have shown how the aggregate genomes of gastrointestinal bacteria provide novel benefits by functioning as the third major genome in mammals along with the nuclear and mitochondrial genomes. Consequently, efforts are underway to elucidate the complexity of the organisms comprising the unique ecosystem of the gastrointestinal tract, as well as those associated with other epidermal surfaces. The current knowledge of the gastrointestinal microbiome, its relationship to human health and disease with a particular focus on mammalian physiology, and efforts to alter its composition as a novel therapeutic approach are reviewed.     

The redox potential, rH and pH values in the gastrointestinal tract of small ruminants

Oxidation-reduction potentials (Eh), pH and rH in the gastrointestinal tract were measured in six goats and two sheep fed on ground barley and hay, with or without the addition of urea. Each ration was supplied for three weeks. The animals were slaughtered after morning feeding, the contents of relevant parts of the gastrointestinal tract were sampled, pH and Eh values were measured and rH values calculated. The range of the oxidation-reduction potential was rather extensive, from -300 to +186 mV. The variability of rH values was smaller, being between 4.6 and 12.9, except for three values. The following linear relationship holds for findings of Eh and pH: Eh (mV) = 292-69.9 pH with a correlation coefficient of r = 0.84. In those parts of the gastrointestinal tract, where the fermentation process occurs (the rumen, caecum and colon), the Eh and rH values are lower than those in the abomasum and duodenum. Urea addition has no effect on the oxidation-reduction equilibrium.     

Adaptation for water balance in the partial gastrointestinal tract of summer flounder

Marine teleosts continually drink and absorb water across the intestine to prevent dehydration. Surprisingly, summer flounder that are missing most of their intestine, due to necrotizing enteritis, maintain osmotic homeostasis. Here, we tested the hypothesis that this remnant gastrointestinal tract undergoes compensatory adaptation for fluid uptake. Flounder (Paralicthys dentatus) with a partial gastrointestinal tract had an emaciated liver. Moisture content of muscle however was similar to healthy cohorts with an intact gastrointestinal tract, indicative of an undisturbed osmoregulatory status. Mass-specific rates of fluid uptake across all segments of the partial gastrointestinal tract were less than or similar to rates in corresponding segments from intact flounder. In contrast, weights (percent of body mass) were doubled in stomach and partial intestine of the remnant gastrointestinal tract. Consequently, total capacity for fluid uptake (microL h(-1) g body mass(-1)) was similar for both groups. The functional capacity of the remnant gastrointestinal tract was therefore of a magnitude sufficient to maintain osmoregulatory ability, further evidencing a critical role of the intestine in salt and water balance of marine teleosts.     

细菌在胃肠道肿瘤发生中的作用及其机制

胃肠道肿瘤具有较高的发病率和死亡率,其防治已成为重要的公共卫生问题。胃肠道内的菌群常参与机体的代谢和免疫反应,协同维持机体的平衡状态。多项研究发现消化道内细菌种类和数目的变化在胃肠道肿瘤的发生和发展中具有重要作用。细菌可通过毒力因子、生物膜、代谢产物等多种因素参与致肿瘤作用,甚至影响化疗药物的疗效,然而,细菌在肿瘤发生中的作用地位尚不明确。因此,本文对细菌致胃肠道肿瘤发生发展的机制进行综述,以期为胃肠道肿瘤的早期防治提供理论依据。     

Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract

Studies have shown that bone marrow cells have the potential to differentiate into a variety of cell types. Here we show that bone marrow cells can repopulate the epithelia of the human gastrointestinal tract. Epithelial cells of male donor origin were distributed in every part of the gastrointestinal tract of female bone marrow transplant recipients. Donor-derived epithelial cells substantially repopulated the gastrointestinal tract during epithelial regeneration after graft-versus-host disease or ulcer formation. Regeneration of gastrointestinal epithelia with donor-derived cells in humans shows a potential clinical application of bone marrow-derived cells for repairing severely damaged epithelia, not only in the gastrointestinal tract but also in other tissues.     

Polyelectrolyte nanoparticles with high drug loading enhance the oral uptake of hydrophobic compounds

In the pharmaceutical industry, orally active compounds are required to have sufficient water solubility to enable dissolution within the gastrointestinal tract prior to absorption. Limited dissolution within the gastrointestinal tract often reduces the bioavailability of hydrophobic drugs. To improve gastrointestinal tract dissolution, nonaqueous solvents are often used in the form of emulsions and microemulsions. Here, we show that oil-free polyelectrolyte nanosystems (micellar dispersions and 100-300 nm particles) prepared from poly(ethylenimines) derivatized with cetyl chains and quaternary ammonium groups are able to encapsulate high levels of hydrophobic drug (0.20 g of drug per g of polymer) for over 9 months, as demonstrated using cyclosporine A (log P = 4.3). The polyelectrolytes facilitate the absorption of hydrophobic drugs within the gastrointestinal tract by promoting drug dissolution and by a hypothesized mechanism involving paracellular drug transport. Polyelectrolyte nanoparticle drug blood levels are similar to those obtained with commercial microemulsion formulations. The polyelectrolytes do not promote absorption by inhibition of the P-glycoprotein efflux pump.     

Aquaporin-6 is expressed along the rat gastrointestinal tract and upregulated by feeding in the small intestine

Background  

Several aquaporins (a family of integral membrane proteins) have been recently identified in the mammalian gastrointestinal tract, and their involvement in the movement of fluid and small solutes has been suggested. In this direction we investigated, in some regions of the rat gastrointestinal tract, the presence and localization of aquaporin-6, given its peculiar function as an ion selective channel.     

Taste receptors in the gastrointestinal tract. II. L-amino acid sensing by calcium-sensing receptors: implications for GI physiology

The extracellular calcium-sensing receptor (CaR) is a multimodal sensor for several key nutrients, notably Ca2+ ions and L-amino acids, and is expressed abundantly throughout the gastrointestinal tract. While its role as a Ca2+ ion sensor is well recognized, its physiological significance as an L-amino acid sensor and thus, in the gastrointestinal tract, as a sensor of protein ingestion is only now coming to light. This review focuses on the CaR's amino acid sensing properties at both the molecular and cellular levels and considers new and putative physiological roles for the CaR in the amino acid-dependent regulation of gut hormone secretion, epithelial transport, and satiety.     

Comparison of Lactobacillus strains with respect to bile salt hydrolase activity, colonization of the gastrointestinal tract, and growth rate of the murine host.

The significance of bile salt hydrolase production by lactobacilli in the microecology of the murine intestinal tract has not been extensively studied previously. Assays of bile salt hydrolase (sodium taurocholate as substrate) associated with cell extracts of five Lactobacillus strains of murine origin gave a range of activities (from 915 nmol of cholate released per mg of protein per 30 min to none detected). All of the strains tested colonized the murine gastrointestinal tract equally well. The growth rates of mice were not affected by colonization of their intestinal tracts by lactobacilli whether or not the bacteria produced bile salt hydrolase.     

Comparison of cellular fatty acid profiles of the microbiota in different gut regions of BALB/c and C57BL/6J mice

The gastrointestinal tracts of developed animals are colonized by an extremely complex and diverse microbial ecosystem. The host and its microbiota are in close interaction with each other, and the hosts genetic characteristics have been suggested to have an influence on the composition of fecal bacteria. However, different sections of gastrointestinal tract harbor microbes typical of each particular section and knowledge of the effect of the hosts genotype on the microbiota in the different parts of the gastrointestinal tract is limited. In this study, mice from two inbred strains, C57BL/6J and BALB/c, were raised in identical conditions. Bacterial samples were collected from four parts of the gastrointestinal tract and analyzed for bacterial fatty acids using gas-liquid chromatography (GLC). Significant differences between the microbiota in the feces, in the cecum, in the small bowel and in the stomach were observed. Cecal samples produced more diverse bacterial fatty acid profiles than any of the other samples, revealing a higher bacterial density and a higher number of bacterial species. Further, a significant difference between the two strains of mice was observed throughout the gastrointestinal tract. These findings indicate that the hosts genotype has an influence on the gastrointestinal microbiota as a whole, and provide further evidence that the cecum is the most species-rich region of the murine gut.     

白鹮胃肠道内分泌细胞的免疫组织化学定位

为了解白的消化生理过程 ,利用ABC免疫组织化学方法 ,对白胃肠道 5种内分泌细胞 :5 -羟色胺 (5 HT)、脑啡肽、P物质、胃动素和抑胃素的分布进行了研究。结果表明 :5 HT细胞主要分布于十二指肠及其以下部位 ,尤其是盲肠和直肠 ;而腺胃、肌胃和幽门中均未发现该类细胞。脑啡肽和P物质细胞数量明显较 5 HT少 ,它们稀疏分布于十二指肠及其以下部位 ,无显著的分布积聚区。抑胃素和胃动素在整个胃肠道中均无分布。分析表明白胃肠道 5种内分泌细胞的分布与其他鸟类相似 ,但与其他脊椎动物明显不同。     

白yuan胃肠道内分泌细胞的免疫组织化学定位

为了解白yuan的消化生理过程,利用ABC免疫组织化学方法,对白yuan胃肠道5种内分泌细胞：5-羟色胺(5-HT)、脑啡肽、P物质、胃动素和抑胃素的分布进行了研究。结果表明：5-HT细胞主要分布于十二指肠及其以下部位,尤其是盲肠和直肠;而腺胃、肌胃和幽门中均未发现该类细胞。脑啡肽和P物质细胞数量明显较5-HT少,它们稀疏分布于十二指肠及其以下部位,无显著的分布积聚区。抑胃素和胃动素在整个胃肠道中均无分布。分析表明白yuan胃肠道5种内分泌细胞的分布与其他鸟类相似,但与其他脊椎动物明显不同。     

Gastrointestinal inflammation: a central component of mucosal defense and repair

The mucosal layer of the gastrointestinal (GI) tract is able to resist digestion by the endogenous substances that we secrete to digest foodstuffs. So-called "mucosal defense" is multi-factorial and can be modulated by a wide range of substances, many of which are classically regarded as inflammatory mediators. Damage to the GI mucosa, and its subsequent repair, are also modulated by various inflammatory mediators. In this article, we provide a review of some of the key inflammatory mediators that modulate GI mucosal defense, injury, and repair. Among the mediators discussed are nitric oxide, polyamines, the eicosanoids (prostaglandins and lipoxins), protease-activated receptors, and cytokines. Many of these endogenous factors, or the enzymes involved in their synthesis, are considered potential therapeutic targets for the treatment of diseases of the digestive tract that are characterized by inflammation and ulceration.