Microbial imbalance in inflammatory bowel disease patients at different taxonomic levels

Background Inflammatory bowel disease (IBD), is a debilitating group of chronic diseases including Crohn’s Disease (CD) and ulcerative colitis (UC), which causes inflammation of the gut and affects millions of people worldwide. At different taxonomic levels, the structure of the gut microbiota is significantly altered in IBD patients compared to that of healthy individuals. However, it is unclear how these IBD-affected bacterial groups are related to other common bacteria in the gut, and how they are connected across different disease conditions at the global scale. Results In this study, using faecal samples from patients with IBD, we show through diversity analysis of the microbial community structure based on the 16S rRNA gene that the gut microbiome of IBD patients is less diverse compared to healthy individuals. Furthermore, we have identified which bacterial groups change in abundance in both CD and UC compared to healthy controls. A substantial imbalance was observed across four major bacterial phyla including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria, which together constitute >98% of the gut microbiota. Next, we reconstructed a bacterial family co-abundance network based on the correlation of abundance profiles obtained from the public gut microbiome data of >22000 samples of faecal and gut biopsies taken from both diseased and healthy individuals. The data was compiled using the EBI metagenomics database [1]. By mapping IBD-altered bacterial families to the network, we show that the bacterial families which exhibit an increased abundance in IBD conditions are not well connected to other groups, implying that these families generally do not coexist together with common gut organisms. Whereas, the bacterial families whose abundance is reduced or did not change in IBD conditions compared to healthy conditions are very well connected to other bacterial groups, suggesting they are highly important groups of bacteria in the gut that can coexist with other bacteria across a range of conditions. Conclusions IBD patients exhibited a less diverse gut microbiome compared to healthy individuals. Bacterial groups which changed in IBD patients were found to be groups which do not co-exist well with common commensal gut bacteria, whereas bacterial groups which did not change in patients with IBD were found to commonly co-exist with commensal gut microbiota. This gives a potential insight into the dynamics of the gut microbiota in patients with IBD

Analisis Unit Cost Pelayanan Rawat Inap Postpartum Di Rumah Sakit Umum Dewi Sartika Dengan Menggunakan Metode Activity Based Costing (ABC) System

Iklim kompetitif tidak hanya terjadi pada Perusahaan yang berorientasi profit, namun juga berdampak padaperusahaan yang berorientasi nonprofit, salah satunya adalah rumah sakit. Rumah sakit yang berada di SulawesiTenggara pada tahun 2014 berjumlah 36, sedangkan kota Kendari memiliki 13 rumah sakit dan harus melayani347.496 penduduk. Hal ini menjadikan persaingan bisnis rumah sakit baik umum maupun swasta kini semakinketat. Salah satu solusi untuk memenangkan persaingan adalah dengan cara menentukan tarif yang lebih rendahdan kualitas atau jasa yang lebih tinggi dari pada pesaing. Solusi tersebut tentunya menjadikan biaya operasionalrumah sakit akan semakin besar sehingga sistem akuntansi manajemen di rumah sakit harus efektif dan efisiensehingga menghasilkan informasi yang akurat dalam pengambilan keputusan. Rumah sakit cenderung masihmenggunakan system akuntansi tradisional yang memiliki distorsi biaya. Penelitian ini menganalisis perhitungantarif rawat inap pelayanan postpartum di RSU Dewi Sartika menggunakan metode activity based costing system.Penelitian ini menggunakan metode deskriptif komparatif dengan pendekatan kuantitatif, data yang digunakanadalah seluruh data keuangan pada Oktober 2015-September 2016 dan aktivitas yang diobservasi yaitu ruangperawatan kelas VIP, kelas I, kelas II, kelas III dan bangsal. Hasil perhitungan menunjukkan hasil yang berbeda daritarif yang diterapkan. Tarif kelas VIP, kelas I dan kelas III lebih rendah dari tarif rumah sakit sedangkan tarif kelas IIdan bangsal lebih tinggi

Mining for nonribosomal peptide synthetase and polyketide synthase genes revealed a high level of diversity in the sphagnum bog metagenome

Sphagnum bog ecosystems are one of the oldest vegetation forms harbouring a specific microbial community, which is known to produce an exceptionally wide variety of bioactive substances. Although the Sphagnum metagenome indicate a rich secondary metabolism, the genes are not yet explored. To analyse non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) the diversity of NRPS and PKS genes in Sphagnum-associated metagenome was investigated by in silico data mining and sequence-based screening (PCR-amplification of 9500 fosmid clones). The in silico Illumina-based metagenomic approach resulted in the identification of 279 NRPS, 346 PKS, as well as 40 PKS-NRPS hybrid gene sequences. Occurrence of NRPS sequences was strongly dominated by the phyla Protebacteria, especially by the genus Burkholderia, while PKS sequences were mainly affiliated to Actinobacteria. Thirteen novel NRPS-related sequences were identified by PCR-amplification screening, displaying amino acid sequence identities of 48 to 91% to annotated sequences of the phyla Proteobacteria, Actinobacteria and Cyanobacteria. Some of the identified metagenomic clones showed closest similarity to peptide synthases from Burkholderia or Lysobacter, which are emerging bacterial sources of yet undescribed bioactive metabolites. This study highlights the role of the extreme natural ecosystems as a promising source for detection of secondary compounds and enzymes, serving as a source for biotechnological applications

Expanding the Repertoire of Carbapenem-Hydrolyzing Metallo-ß-Lactamases by Functional Metagenomic Analysis of Soil Microbiota

Carbapenemases are bacterial enzymes that hydrolyze carbapenems, a group of last-resort β-lactam antibiotics used for treatment of severe bacterial infections. They belong to three β-lactamase classes based amino acid sequence (A, B, and D). The aim of this study was to elucidate occurrence, diversity and functionality of carbapenemase-encoding genes in soil microbiota by functional metagenomics. Ten plasmid libraries were generated by cloning metagenomic DNA from agricultural (n = 6) and grassland (n = 4) soil into Escherichia coli. The libraries were cultured on amoxicillin-containing agar and up to 100 colonies per library were screened for carbapenemase production by CarbaNP test. Presumptive carbapenemases were characterized with regard to DNA sequence, minimum inhibitory concentration (MIC) of β-lactams, and imipenem hydrolysis. Nine distinct class B carbapenemases, also known as metallo-beta-lactamases (MBLs), were identified in six soil samples, including two subclass B1 (GRD23-1 and SPN79-1) and seven subclass B3 (CRD3-1, PEDO-1, GRD33-1, ESP-2, ALG6-1, ALG11-1, and DHT2-1). Except PEDO-1 and ESP-2, these enzymes were distantly related to any previously described MBLs (33 to 59% identity). RAIphy analysis indicated that six enzymes (CRD3-1, GRD23-1, DHT2-1, SPN79-1, ALG6-1, and ALG11-1) originated from Proteobacteria, two (PEDO-1 and ESP-2) from Bacteroidetes and one (GRD33-1) from Gemmatimonadetes. All MBLs detected in soil microbiota were functional when expressed in E. coli, resulting in detectable imipenem-hydrolyzing activity and significantly increased MICs of clinically relevant β-lactams. Interestingly, the MBLs yielded by functional metagenomics generally differed from those detected in the same soil samples by antibiotic selective culture, showing that the two approaches targeted different subpopulations in soil microbiota. © 2016 Gudeta, Bortolaia, Pollini, Docquier, Rossolini, Amos, Wellington and Guardabassi.Grant HEALTH-F3-2011-282004(EvoTAR

Designing and implementing an assay for the detection of rare and divergent NRPS and PKS clones in European, Antarctic and Cuban soils

The ever increasing microbial resistome means there is an urgent need for new antibiotics. Metagenomics is an underexploited tool in the field of drug discovery. In this study we aimed to produce a new updated assay for the discovery of biosynthetic gene clusters encoding bioactive secondary metabolites. PCR assays targeting the polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) were developed. A range of European soils were tested for their biosynthetic potential using clone libraries developed from metagenomic DNA. Results revealed a surprising number of NRPS and PKS clones with similarity to rare Actinomycetes. Many of the clones tested were phylogenetically divergent suggesting they were fragments from novel NRPS and PKS gene clusters. Soils did not appear to cluster by location but did represent NRPS and PKS clones of diverse taxonomic origin. Fosmid libraries were constructed from Cuban and Antarctic soil samples; 17 fosmids were positive for NRPS domains suggesting a hit rate of less than 1 in 10 genomes. NRPS hits had low similarities to both rare Actinobacteria and Proteobacteria; they also clustered with known antibiotic producers suggesting they may encode for pathways producing novel bioactive compounds. In conclusion we designed an assay capable of detecting divergent NRPS and PKS gene clusters from the rare biosphere; when tested on soil samples results suggest the majority of NRPS and PKS pathways and hence bioactive metabolites are yet to be discovere

Manipulating the microbiome : an alternative treatment for bile acid diarrhoea

Bile acid diarrhoea (BAD) is a widespread gastrointestinal disease that is often misdiagnosed as irritable bowel syndrome and is estimated to affect 1% of the United Kingdom (UK) population alone. BAD is associated with excessive bile acid synthesis secondary to a gastrointestinal or idiopathic disorder (also known as primary BAD). Current licensed treatment in the UK has undesirable effects and has been the same since BAD was first discovered in the 1960s. Bacteria are essential in transforming primary bile acids into secondary bile acids. The profile of an individual’s bile acid pool is central in bile acid homeostasis as bile acids regulate their own synthesis. Therefore, microbiome dysbiosis incurred through changes in diet, stress levels and the introduction of antibiotics may contribute to or be the cause of primary BAD. This literature review focuses on primary BAD, providing an overview of bile acid metabolism, the role of the human gut microbiome in BAD and the potential options for therapeutic intervention in primary BAD through manipulation of the microbiome

Corn Yield Potential and Optimal Soil Productivity in Irrigated Corn/Soybean Systems

In 1999, an interdisciplinary research team at the University of Nebraska established a field experiment to (1) quantify and understand the yield potential of corn and soybean under irrigated conditions, (2) identify efficient crop management practices to achieve yields that approach potential levels, and (3) determine the energy use efficiency, global warming and soil C-sequestration potential of intensively managed corn systems. The experiment compares systems that represent different levels of management intensity expressed as combinations of crop rotation (continuous corn, corn-soybean), plant density (low, medium, high) and nutrient management (recommended best management vs. intensive management). Detailed measurements include soil nutrient dynamics and C balance, crop growth and development, nutrient uptake and components of yield of corn and soybean, radiation use efficiency, soil surface fluxes of greenhouse gases, root biomass, C inputs through crop residues, translocation of non-structural carbohydrates, and amount, composition and activity of the microbial biomass. Selected results for corn are presented

Corn Yield Potential and Optimal Soil Productivity in Irrigated Corn/Soybean Systems

In 1999, an interdisciplinary research team at the University of Nebraska established a field experiment to (1) quantify and understand the yield potential of corn and soybean under irrigated conditions, (2) identify efficient crop management practices to achieve yields that approach potential levels, and (3) determine the energy use efficiency, global warming and soil C-sequestration potential of intensively managed corn systems. The experiment compares systems that represent different levels of management intensity expressed as combinations of crop rotation (continuous corn, corn-soybean), plant density (low, medium, high) and nutrient management (recommended best management vs. intensive management). Detailed measurements include soil nutrient dynamics and C balance, crop growth and development, nutrient uptake and components of yield of corn and soybean, radiation use efficiency, soil surface fluxes of greenhouse gases, root biomass, C inputs through crop residues, translocation of non-structural carbohydrates, and amount, composition and activity of the microbial biomass. Selected results for corn are presented

Genetic Determination and Linkage Mapping of Plasmodium falciparum Malaria Related Traits in Senegal

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10−4, Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved

Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in Escherichia coli

Obtaining an in-depth understanding of the arms races between peptides comprising the innate immune response and bacterial pathogens is of fundamental interest and will inform the development of new antibacterial therapeutics. We investigated whether a whole organism view of antimicrobial peptide (AMP) challenge on Escherichia coli would provide a suitably sophisticated bacterial perspective on AMP mechanism of action. Selecting structurally and physically related AMPs but with expected differences in bactericidal strategy, we monitored changes in bacterial metabolomes, morphological features and gene expression following AMP challenge at sub-lethal concentrations. For each technique, the vast majority of changes were specific to each AMP, with such a plastic response indicating E. coli is highly capable of discriminating between specific antibiotic challenges. Analysis of the ontological profiles generated from the transcriptomic analyses suggests this approach can accurately predict the antibacterial mode of action, providing a fresh, novel perspective for previous functional and biophysical studies