Liver cirrhosis is the pathologic end stage of chronic liver disease. Increasing evidence suggests that gut flora is implicated in the pathogenesis of liver cirrhosis complications. The aim of this study was to characterize the fecal microbial communities in patients with liver cirrhosis in comparison with healthy individuals. We recruited 36 patients with liver cirrhosis and 24 healthy controls. The fecal microbial community was analyzed by way of 454 pyrosequencing of the 16S ribosomal RNA V3 region followed by real-time quantitative polymerase chain reaction. Community-wide changes of fecal microbiota in liver cirrhosis were observed compared with healthy controls. The proportion of phylum Bacteroidetes was significantly reduced (P 5 0.008), whereas Proteobacteria and Fusobacteria were highly enriched in the cirrhosis group (P 5 0.001 and 0.002, respectively). Enterobacteriaceae (P 5 0.001), Veillonellaceae (P 5 0.046), and Streptococcaceae (P 5 0.001) were prevalent in patients with cirrhosis at the family level. A positive correlation was observed between Child-Turcotte-Pugh (CTP) score and Streptococcaceae (R 5 0.386, P 5 0.02). Lachnospiraceae decreased significantly in patients with cirrhosis (P 5 0.004) and correlated negatively with CTP score (R 5 20.49, P 5 0.002). Using partial least square discriminate analysis, we identified 149 operational taxonomic units (OTUs) as key phylotypes that responded to cirrhosis, most of which were Lachnospiraceae (65 OTUs), Streptococcaceae (23 OTUs), and Veillonellaceae (21 OTUs). Conclusion: Fecal microbial communities are distinct in patients with cirrhosis compared with healthy individuals. The prevalence of potentially pathogenic bacteria, such as Enterobacteriaceae and Streptococcaceae, with the reduction of beneficial populations such as Lachnospiraceae in patients with cirrhosis may affect prognosis. (HEPATOLOGY 2011;54:562-572)

A r t i c l e sThe dog tapeworm E. granulosus is one of a group of medically important parasitic helminths of the family Taeniidae (Platyhelminthes; Cestoda; Cyclophyllidea) that infect at least 50 million people globally 1 . Its life cycle involves two mammals, including an intermediate host, usually a domestic or wild ungulate (humans are accidental intermediate hosts) and a canine-definitive host, such as the domestic dog. The larval (metacestode) stage causes hydatidosis (cystic hydatid disease; cystic echinococcosis), a chronic cyst-forming disease in the intermediate (human) host. Currently, up to 3 million people are infected with E. granulosus 2,3 , and, in some areas, 10% of the population has detectable hydatid cysts by abdominal ultrasound and chest X-ray 4,5 .E. granulosus has no gut, circulatory or respiratory organs. It is monoecious, producing diploid eggs that give rise to ovoid embryos, the oncospheres. Strobilization is a notable feature of cestode biology, whereby proglottids bud distally from the anterior scolex, resulting in the production of tandem reproductive units exhibiting increasing degrees of development. A unique characteristic of the larvae (protoscoleces, PSCs) within the hydatid cyst is an ability to develop bidirectionally into an adult worm in the dog gastrointestinal tract or into a secondary hydatid cyst in the intermediate (human) host, a process triggered by bile acids 6 . Another distinct feature of E. granulosus is its capacity to infect and adapt to a large number of mammalian species as intermediate hosts, which has contributed to its cosmopolitan global distribution.Here we report the sequence and analysis of the E. granulosus genome. Comprising nine pairs of chromosomes 7 , it is one of the first cestode genomes to be sequenced and complements the recent publication by Tsai et al. 8 of a high-quality genome for Echinococcus multilocularis (the cause of alveolar echinococcosis), together with draft genomes of three other tapeworm species including E. granulosus. Our study provides insights into the biology, development, differentiation, evolution and host interaction of E. granulosus and has identified a range of drug and vaccine targets that can facilitate the development of new intervention tools for hydatid treatment and control. Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCa v b 1 may be associated with praziquantel sens...

The human gut microbiota is a complex system that is essential to the health of the host. Increasing evidence suggests that the gut microbiota may play an important role in the pathogenesis of colorectal cancer (CRC). In this study, we used pyrosequencing of the 16S rRNA gene V3 region to characterize the fecal microbiota of 19 patients with CRC and 20 healthy control subjects. The results revealed striking differences in fecal microbial population patterns between these two groups. Partial least-squares discriminant analysis showed that 17 phylotypes closely related to Bacteroides were enriched in the gut microbiota of CRC patients, whereas nine operational taxonomic units, represented by the butyrate-producing genera Faecalibacterium and Roseburia, were significantly less abundant. A positive correlation was observed between the abundance of Bacteroides species and CRC disease status (R = 0.462, P = 0.046 < 0.5). In addition, 16 genera were significantly more abundant in CRC samples than in controls, including potentially pathogenic Fusobacterium and Campylobacter species at genus level. The dysbiosis of fecal microbiota, characterized by the enrichment of potential pathogens and the decrease in butyrate-producing members, may therefore represent a specific microbial signature of CRC. A greater understanding of the dynamics of the fecal microbiota may assist in the development of novel fecal microbiome-related diagnostic tools for CRC.

BackgroundBacterial vaginosis (BV) is an ecological disorder of the vaginal microbiota that affects millions of women annually, and is associated with numerous adverse health outcomes including pre-term birth and the acquisition of sexually transmitted infections. However, little is known about the overall structure and composition of vaginal microbial communities; most of the earlier studies focused on predominant vaginal bacteria in the process of BV. In the present study, the diversity and richness of vaginal microbiota in 50 BV positive and 50 healthy women from China were investigated using culture-independent PCR-denaturing gradient gel electrophoresis (DGGE) and barcoded 454 pyrosequencing methods, and validated by quantitative PCR.ResultsOur data demonstrated that there was a profound shift in the absolute and relative abundances of bacterial species present in the vagina when comparing populations associated with healthy and diseased conditions. In spite of significant interpersonal variations, the diversity of vaginal microbiota in the two groups could be clearly divided into two clusters. A total of 246,359 high quality pyrosequencing reads was obtained for evaluating bacterial diversity and 24,298 unique sequences represented all phylotypes. The most predominant phyla of bacteria identified in the vagina belonged to Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria. The higher number of phylotypes in BV positive women over healthy is consistent with the results of previous studies and a large number of low-abundance taxa which were missed in previous studies were revealed. Although no single bacterium could be identified as a specific marker for healthy over diseased conditions, three phyla - Bacteroidetes, Actinobacteria and Fusobacteria, and eight genera including Gardnerella, Atopobium, Megasphaera, Eggerthella, Aerococcus, Leptotrichia/Sneathia, Prevotella and Papillibacter were strongly associated with BV (p < 0.05). These genera are potentially excellent markers and could be used as targets for clinical BV diagnosis by molecular approaches.ConclusionsThe data presented here have clearly profiled the overall structure of vaginal communities and clearly demonstrated that BV is associated with a dramatic increase in the taxonomic richness and diversity of vaginal microbiota. The study also provides the most comprehensive picture of the vaginal community structure and the bacterial ecosystem, and significantly contributes to the current understanding of the etiology of BV.

Increasing evidence suggests that perturbations in the intestinal microbiota composition of infants are implicated in the pathogenesis of food allergy (FA), while the actual structure and composition of the intestinal microbiota in human beings with FA remain unclear. Microbial diversity and composition were analyzed with parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V1-V3 regions in the feces of 34 infants with FA (17 IgE mediated and 17 non-IgE mediated) and 45 healthy controls. Here, we showed that several key FA-associated bacterial phylotypes, but not the overall microbiota diversity, significantly changed in infancy fecal microbiota with FA and were associated with the development of FA. The proportion of abundant Bacteroidetes, Proteobacteria, and Actinobacteria phyla were significantly reduced, while the Firmicutes phylum was highly enriched in the FA group (P < 0.05). Abundant Clostridiaceae 1 organisms were prevalent in infants with FA at the family level (P ‫؍‬ 0.016). FA-enriched phylotypes negatively correlated with interleukin-10, for example, the genera Enterococcus and Staphylococcus. Despite profound interindividual variability, levels of 20 predominant genera were significantly different between the FA and healthy control groups (P < 0.05). Infants with IgE-mediated FA had increased levels of Clostridium sensu stricto and Anaerobacter and decreased levels of Bacteroides and Clostridium XVIII (P < 0.05). A positive correlation was observed between Clostridium sensu stricto and serum-specific IgE (R ‫؍‬ 0.655, P < 0.001). The specific microbiota signature could distinguish infants with IgE-mediated FA from non-IgE-mediated ones. Detailed microbiota analysis of a well-characterized cohort of infants with FA showed that dysbiosis of fecal microbiota with several FA-associated key phylotypes may play a pathogenic role in FA.

Oral microbiota plays a vital role in maintaining the homeostasis of oral cavity. Dental caries are among the most common oral diseases in children and pathogenic bacteria contribute to the development of the disease. However, the overall structure of bacterial communities in the oral cavity from children with dental caries has not been explored deeply heretofore. We used high-throughput barcoded pyrosequencing and PCR-denaturing gradient gel electrophoresis (DGGE) to examine bacterial diversity of oral microbiota in saliva and supragingival plaques from 60 children aged 3 to 6 years old with and without dental caries from China. The multiplex barcoded pyrosequencing was performed in a single run, with multiple samples tagged uniquely by multiplex identifiers. As PCR-DGGE analysis is a conventional molecular ecological approach, this analysis was also performed on the same samples and the results of both approaches were compared. A total of 186,787 high-quality sequences were obtained for evaluating bacterial diversity and 41,905 unique sequences represented all phylotypes. We found that the oral microbiota in children was far more diverse than previous studies reported, and more than 200 genera belonging to ten phyla were found in the oral cavity. The phylotypes in saliva and supragingival plaques were significantly different and could be divided into two distinct clusters (p < 0.05). The bacterial diversity in oral microbiome analyzed by PCR-DGGE and barcoded pyrosequencing was employed to cross validate the data sets. The genera of Streptococcus, Veillonella, Actinomyces, Granulicatella, Leptotrichia, and Thiomonas in plaques were significantly associated with dental caries (p < 0.05). The results showed that there was no one specific pathogen but rather pathogenic populations in plaque that significantly correlated with dental caries. The enormous diversity of oral microbiota allowed for a better understanding of oral microecosystem, and these pathogenic populations in plaque provide new insights into the etiology of dental caries and suggest new targets for interventions of the disease.

Of the two cultivated species of allopolyploid cotton, Gossypium barbadense produces extra-long fibers for the production of superior textiles. We sequenced its genome (AD)2 and performed a comparative analysis. We identified three bursts of retrotransposons from 20 million years ago (Mya) and a genome-wide uneven pseudogenization peak at 11–20 Mya, which likely contributed to genomic divergences. Among the 2,483 genes preferentially expressed in fiber, a cell elongation regulator, PRE1, is strikingly At biased and fiber specific, echoing the A-genome origin of spinnable fiber. The expansion of the PRE members implies a genetic factor that underlies fiber elongation. Mature cotton fiber consists of nearly pure cellulose. G. barbadense and G. hirsutum contain 29 and 30 cellulose synthase (CesA) genes, respectively; whereas most of these genes (>25) are expressed in fiber, genes for secondary cell wall biosynthesis exhibited a delayed and higher degree of up-regulation in G. barbadense compared with G. hirsutum, conferring an extended elongation stage and highly active secondary wall deposition during extra-long fiber development. The rapid diversification of sesquiterpene synthase genes in the gossypol pathway exemplifies the chemical diversity of lineage-specific secondary metabolites. The G. barbadense genome advances our understanding of allopolyploidy, which will help improve cotton fiber quality.

Super-enhancers are important for controlling and defining the expression of cell-specific genes. With research on human disease and biological processes, human H3K27ac ChIP-seq datasets are accumulating rapidly, creating the urgent need to collect and process these data comprehensively and efficiently. More importantly, many studies showed that super-enhancer-associated single nucleotide polymorphisms (SNPs) and transcription factors (TFs) strongly influence human disease and biological processes. Here, we developed a comprehensive human super-enhancer database (SEdb, http://www.licpathway.net/sedb) that aimed to provide a large number of available resources on human super-enhancers. The database was annotated with potential functions of super-enhancers in the gene regulation. The current version of SEdb documented a total of 331 601 super-enhancers from 542 samples. Especially, unlike existing super-enhancer databases, we manually curated and classified 410 available H3K27ac samples from >2000 ChIP-seq samples from NCBI GEO/SRA. Furthermore, SEdb provides detailed genetic and epigenetic annotation information on super-enhancers. Information includes common SNPs, motif changes, expression quantitative trait locus (eQTL), risk SNPs, transcription factor binding sites (TFBSs), CRISPR/Cas9 target sites and Dnase I hypersensitivity sites (DHSs) for in-depth analyses of super-enhancers. SEdb will help elucidate super-enhancer-related functions and find potential biological effects.