Characterization of gut microbiota composition in HIV-infected patients with metabolic syndrome

Journal of Physiology and Biochemistry - The presence of metabolic syndrome (MS) per se or its separated components in HIV-infected patients contributes to an accelerated aging and increased...     

肥胖相关的肠道微生物群落结构动力学与功能解析研究

肥胖及相关的慢性代谢性疾病近年来已经成为威胁全球的公共健康问题。越来越多的证据表明,在宿主的营养、免疫和代谢中有不可替代的作用的肠道菌群不仅可以通过调节宿主脂肪吸收存储相关的基因,影响后者的能量平衡,更重要的是其结构失调导致宿主循环系统中内毒素增加,诱发慢性、低水平炎症,导致肥胖和胰岛素抵抗。运用微生物分子生态学、元基因组学和代谢组学的方法,揭示与代谢性疾病相关的菌群结构失调,并鉴定出相关的特定细菌类群及其功能,使得通过以菌群为靶点的营养干预手段防止慢性代谢性疾病成为可能,将带来代谢性疾病预防和控制策略的革命性的变化。     

Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome

(1)H NMR spectroscopy of aqueous fecal extracts has been used to investigate differences in metabolic activity of gut microbiota in patients with ulcerative colitis (UC) (n = 13), irritable bowel syndrome (IBS) (n = 10), and healthy controls (C) (n = 22). Up to four samples per individual were collected over 2 years giving a total of 124 samples. Multivariate discriminant analysis, based on NMR data from all three groups, was able to predict UC and C group membership with good sensitivity and specificity; classification of IBS samples was less successful and could not be used for diagnosis. Trends were detected toward increased taurine and cadaverine levels in UC with increased bile acid and decreased branched chain fatty acids in IBS relative to controls; changes in short chain fatty acids and amino acids were not significant. Previous PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis of the same fecal material had shown alterations of the gut microbiota when comparing UC and IBS groups with controls. Hierarchical cluster analysis showed that DGGE profiles from the same individual were stable over time, but NMR spectra were more variable; canonical correlation analysis of NMR and DGGE data partly separated the three groups and revealed a correlation between the gut microbiota profile and metabolite composition.     

按蚊肠道微生物及其在阻断疟疾传播上的应用

按蚊体内,尤其是中肠内定殖着大量的微生物群落。肠道菌群通过与按蚊的长期协同进化形成了相互依存的共生关系。肠道共生菌参与调节按蚊的多种生命活动,对于维持按蚊的健康发挥着重要作用,已经成为一个与宿主按蚊密不可分的重要"器官"。研究表明,肠道共生菌在按蚊物质代谢、营养、发育、生殖、免疫调控和免疫防御等生理过程中发挥着重要的调节作用。蚊虫是疟疾、登革、寨卡等多种疾病的传播媒介,而肠道共生菌对寄生虫和病毒在蚊虫肠道内的发育和感染具有重要影响,因此研究蚊虫与共生菌的相互作用有着重要的理论和实践意义。本文将对按蚊肠道共生菌的多样性、生物学功能、与宿主相互作用的机制及其在防治疟疾上的应用进展进行综述,并对未来的研究提出展望。     

Disruption of the termite gut microbiota and its prolonged consequences for fitness

The disruption of host-symbiont interactions through the use of antibiotics can help elucidate microbial functions that go beyond short-term nutritional value. Termite gut symbionts have been studied extensively, but little is known about their impact on the termite's reproductive output. Here we describe the effect that the antibiotic rifampin has not only on the gut microbial diversity but also on the longevity, fecundity, and weight of two termite species, Zootermopsis angusticollis and Reticulitermes flavipes. We report three key findings: (i) the antibiotic rifampin, when fed to primary reproductives during the incipient stages of colony foundation, causes a permanent reduction in the diversity of gut bacteria and a transitory effect on the density of the protozoan community; (ii) rifampin treatment reduces oviposition rates of queens, translating into delayed colony growth and ultimately reduced colony fitness; and (iii) the initial dosages of rifampin had severe long-term fitness effects on Z. angusticollis. Taken together, our findings demonstrate that the antibiotic-induced perturbation of the microbial community is associated with prolonged reductions in longevity and fecundity. A causal relationship between these changes in the gut microbial population structures and fitness is suggested by the acquisition of opportunistic pathogens and incompetence of the termites to restore a pretreatment, native microbiota. Our results indicate that antibiotic treatment significantly alters the termite's microbiota, reproduction, colony establishment, and ultimately colony growth and development. We discuss the implications for antimicrobials as a new application to the control of termite pest species.     

Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome

The gut microbiota is increasingly considered as a symbiotic partner for the maintenance of health. The homeostasis of the gut microbiota is dependent on host characteristics (age, gender, genetic background...), environmental conditions (stress, drugs, gastrointestinal surgery, infectious and toxic agents...). Moreover, it is dependent on the day-to-day dietary changes. Experimental data in animals, but also observational studies in obese patients, suggest that the composition of the gut microbiota is a factor characterizing obese versus lean individuals, diabetic versus non diabetic patients, or patients presenting hepatic diseases such as non alcoholic steatohepatitis. Interestingly, the changes in the gut microbes can be reversed by dieting and related weight loss. The qualitative and quantitative changes in the intake of specific food components (fatty acids, carbohydrates, micronutrients, prebiotics, probiotics), have not only consequences on the gut microbiota composition, but may modulate the expression of genes in host tissues such as the liver, adipose tissue, intestine, muscle. This in turn may drive or lessen the development of fat mass and metabolic disturbances associated with the gut barrier function and the systemic immunity. The relevance of the prebiotic or probiotic approaches in the management of obesity in humans is supported by few intervention studies in humans up to now, but the experimental data obtained with those compounds help to elucidate novel potential molecular targets relating diet with gut microbes. The metagenomic and integrative metabolomic approaches could help elucidate which bacteria, among the trillions in human gut, or more specifically which activities/genes, could participate to the control of host energy metabolism, and could be relevant for future therapeutic developments.     

Beneficial modulation of the gut microbiota

The human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.     

Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits

The gastrointestinal tract harbors a complex and diverse microbiota that has an important role in host metabolism. Microbial diversity is influenced by a combination of environmental and host genetic factors and is associated with several polygenic diseases. In this study we combined next-generation sequencing, genetic mapping, and a set of physiological traits of the BXD mouse population to explore genetic factors that explain differences in gut microbiota and its impact on metabolic traits. Molecular profiling of the gut microbiota revealed important quantitative differences in microbial composition among BXD strains. These differences in gut microbial composition are influenced by host-genetics, which is complex and involves many loci. Linkage analysis defined Quantitative Trait Loci (QTLs) restricted to a particular taxon, branch or that influenced the variation of taxa across phyla. Gene expression within the gastrointestinal tract and sequence analysis of the parental genomes in the QTL regions uncovered candidate genes with potential to alter gut immunological profiles and impact the balance between gut microbial communities. A QTL region on Chr 4 that overlaps several interferon genes modulates the population of Bacteroides, and potentially Bacteroidetes and Firmicutes-the predominant BXD gut phyla. Irak4, a signaling molecule in the Toll-like receptor pathways is a candidate for the QTL on Chr15 that modulates Rikenellaceae, whereas Tgfb3, a cytokine modulating the barrier function of the intestine and tolerance to commensal bacteria, overlaps a QTL on Chr 12 that influence Prevotellaceae. Relationships between gut microflora, morphological and metabolic traits were uncovered, some potentially a result of common genetic sources of variation.     

PPAR家族及其与代谢综合征的关系

过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors,PPARs)是配体激活的转录因子核受体超家族成员之一。目前已知有三种亚型：PPARα、-β／δ和-γ。它们在脂肪生成、脂质代谢、胰岛素敏感性、炎症和血压调节中起着关键作用,因而近年来倍受关注。越来越多的研究表明,PPARs与代谢综合征,包括胰岛素抵抗、糖耐量受损、2型糖尿病、肥胖、高脂血症、高血压病、动脉粥样硬化和蛋白尿之间存在因果关系。重要的是,PPARα的激动剂如贝丁酸类降脂药(Fibrate)和PPARγ的激动剂如噻唑烷二酮(Thiazolidinedione,TZD)均已被证实有改善代谢综合征的作用。此外,三种PPAR亚型在2型糖尿病及糖尿病肾病的发展中均有重要作用。不断增加的证据提示,PPARs有可能成为代谢综合征及其相关并发症的潜在治疗靶点。本文将就PPARs的生物学活性、配体选择性和生理学功能作一综述,并对其在代谢综合征发病机制中的作用和PPAR配体对2型糖尿病的治疗效用进行重点讨论。     

Human gut microbiota and bifidobacteria: from composition to functionality

The human gut is the home of an estimated 10(18) bacterial cells, many of which are uncharacterized or unculturable. Novel culture-independent approaches have revealed that the majority of the human gut microbiota consists of members of the phyla Bacteroidetes and Firmicutes. Nevertheless the role of bifidobacteria in gut ecology illustrates the importance of Actinomycetes and other Actinobacteria that may be underestimated. The human gut microbiota represents an extremely complex microbial community the collective genome of which, the microbiome, encodes functions that are believed to have a significant impact on human physiology. The microbiome is assumed to significantly enhance the metabolism of amino and glycan acids, the turnover of xenobiotics, methanogenesis and the biosynthesis of vitamins. Co-colonisation of the gut commensals Bifidobacterium longum and Bacteroides thetaiotaomicron in a murine model system revealed that the presence of bifidobacteria induced an expansion in the diversity of polysaccharides targeted for degradation by Bacteroides and also induced host genes involved in innate immunity. In addition, comparative analysis of individual human gut microbiomes has revealed various strategies that the microbiota use to adapt to the intestinal environment while also pointing to the existence of a distinct infant and adult-type microbiota.     

肠道菌群与代谢研究进展

从出生伊始肠道菌群就依赖于宿主的基因组、营养和生活方式而变化的,与宿主共同进化发展.肠道菌群参与调控其宿主的多种代谢途径,包括宿主的免疫、营养,并且极大地影响宿主的物质能量代谢及与物质能量代谢相关疾病的发生与发展过程.同时又与多个器官共同作用,在宿主的代谢、信息传递,疾病的感染与防御方面起非常重要的作用.深入了解肠道菌群在其参与代谢的具体作用,对理解物质能量代谢相关疾病病因、优化治疗策略、调节肠道菌群、防治疾病和提高宿主健康水平具有重要作用.本研究对人类肠道菌群的形成、物质能量代谢、代谢相关疾病及其防治等方面的研究进展加以综述.     

Structural changes of gut microbiota in Parkinson's disease and its correlation with clinical features

The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16 S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia(P=0.018),Faecalibacterium(P=0.048) and Ruminococcus(P=0.019) were significantly decreased in PD compared to healthy controls.The putative pathobionts from the genera Escherichia-Shigella(P=0.038), Streptococcus(P=0.01), Proteus(P=0.022), and Enterococcus(P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.     

Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice

We investigated the relationship between gut health, visceral fat dysfunction and metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or high saturated fat diet (HFD). Circulating glucose, insulin and inflammatory markers were measured. Proximal colon barrier function was assessed by measuring transepithelial resistance and mRNA expression of tight-junction proteins. Gut microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA levels were measured in proximal colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration (F4/80⁺) was assessed using immunohistochemical staining. HFD mice had a higher insulin/glucose ratio (P = 0.020) and serum levels of serum amyloid A3 (131%; P = 0.008) but reduced circulating adiponectin (64%; P = 0.011). In proximal colon of HFD mice compared to mice fed the control diet, transepithelial resistance and mRNA expression of zona occludens 1 were reduced by 38% (P<0.001) and 40% (P = 0.025) respectively and TNF-α mRNA level was 6.6-fold higher (P = 0.037). HFD reduced Lactobacillus (75%; P<0.001) but increased Oscillibacter (279%; P = 0.004) in fecal microbiota. Correlations were found between abundances of Lactobacillus (r = 0.52; P = 0.013) and Oscillibacter (r = −0.55; P = 0.007) with transepithelial resistance of the proximal colon. HFD increased macrophage infiltration (58%; P = 0.020), TNF-α (2.5-fold, P<0.001) and IL-6 mRNA levels (2.5-fold; P = 0.008) in mesenteric fat. Increased macrophage infiltration in epididymal fat was also observed with HFD feeding (71%; P = 0.006) but neither TNF-α nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed no signs of inflammation in HFD mice. The current results implicate gut dysfunction, and attendant inflammation of contiguous adipose, as salient features of the metabolic dysregulation of diet-induced obesity.     

Bacterial interspecies quorum sensing in the mammalian gut microbiota

The mammalian gastrointestinal tract harbors a diverse and complex resident bacterial community, which interacts with the host in many beneficial processes required for optimal host health. We are studying the importance of bacterial cell-cell communication mediated by the interspecies quorum-sensing signal autoinducer-2 (AI-2) in the beneficial properties of the gut microbiota. Our recent work provided the first evidence that AI-2 produced by Escherichia coli can influence the species composition of this community in the mouse gut. We showed that, under conditions of microbiota imbalances induced by antibiotic treatments, E. coli, which increases intestinal AI-2 levels, not only had an effect on the overall structure of the microbiota community, but specifically favored the expansion of the Firmicutes phylum. Because the Firmicutes are very important for many gut functions and were the group of bacteria most severely affected by antibiotic treatment with streptomycin, we are addressing the possibility that AI-2 can influence the balance of the major bacterial groups in the gut and promote recovery of gut homeostasis. Overall, we want to understand how bacterial chemical signaling shapes the multi-species bacterial communities in the mammalian gut and how these communities affect host physiology.     

Differences in the gut microbiota between Cercopithecinae and Colobinae in captivity

The gut microbiome of captive primates can provide a window into their health and disease status. The diversity and composition of gut microbiota are influenced by not only host phylogeny, but also host diet. Old World monkeys (Cercopithecidae) are divided into two subfamilies: Cercopithecinae and Colobinae. The diet and physiological digestive features differ between these two subfamilies. Accordingly, highthroughput sequencing was used to examine gut microbiota differences between these two subfamilies, using data from 29 Cercopithecinae individuals and 19 Colobinae individuals raised in captivity. Through a comparative analysis of operational taxonomic units (OTUs), significant differences in the diversity and composition of gut microbiota were observed between Cercopithecinae and Colobinae. In particular, the gut microbiota of captive Old World monkeys clustered strongly by the two subfamilies. The Colobinae microbial diversity was higher than that of Cercopithecinae. Additionally, Firmicutes, Lactobacillaceae, Veillonellaceae, and Prevotella abundance were higher in Cercopithecinae, while Bacteroidetes, Ruminococcaceae, Christensenellaceae, Bacteroidaceae, and Acidaminococcaceae abundance were higher in Colobinae. PICRUSt analysis revealed that the predicted metagenomes of metabolic pathways associated with proteins, carbohydrates, and amino acids were significantly higher in Colobinae. In the context of host phylogeny, these differences between Cercopithecinae and Colobinae could reflect adaptations associated with their respective diets. This well-organized dataset is a valuable resource for future related research on primates and gut microbiota. Moreover, this study may provide useful insight into animal management practices and primate conservation.