The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

/pdf/expert-consensus-document-the-international-scientific-1zd5d1fmxy.pdf

Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

/pdf/neuroinflammation-in-alzheimer-s-disease-36czdowiut.pdf

Neuroinflammation in Alzheimer's disease

KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.

http://science.sciencemag.org/content/sci/359/6371/91.full.pdf

Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

Erhebung der Forschungsstrukturen in der Unfallchirurgie

Glacier melt-down changes habitat characteristics and unique microbial community composition and physiology in Alpine lakes sediments.

We report a droplet microfluidic method to target and sort individual cells directly from complex microbiome samples, and to prepare these cells for bulk whole genome sequencing without cultivation. We characterize this approach by recovering bacteria spiked into human stool samples at a ratio as low as 1:250 and by successfully enriching endogenous Bacteroides vulgatus to the level required for de-novo assembly of high-quality genomes. While microbiome strains are increasingly demanded for biomedical applications, the vast majority of species and strains are uncultivated and without reference genomes. We address this shortcoming by encapsulating complex microbiome samples directly into microfluidic droplets and amplify a target-specific genomic fragment using a custom molecular TaqMan probe. We separate those positive droplets by droplet sorting, selectively enriching single target strain cells. Finally, we present a protocol to purify the genomic DNA while specifically removing amplicons and cell debris for high-quality genome sequencing.

Enrichment of gut microbiome strains for cultivation-free genome sequencing using droplet microfluidics

Knochentumore im Bereich der Ferse sind selten, Weichteiltumore noch seltener. Dennoch sollte bei länger anhaltenden Fersenschmerzen immer ein Tumor als Ursache ausgeschlossen werden. Gutartige Tumore überwiegen in der Anzahl deutlich, wobei Kalkaneuszysten den Hauptteil ausmachen. Die häufigsten malignen Knochentumore sind Chondrosarkome, Osteosarkome und das Ewing Sarkom. Einige Entitäten verhalten sich ähnlich wie an den anderen Skelettabschnitten, andere weisen im Fußbereich Besonderheiten auf. Die Diagnose wird in der Regel mittels konventionellem Röntgen, häufig ergänzt durch eine MRT-Untersuchung und ggf. eine CT, gestellt. Eine Sicherung der definitiven Diagnose erfolgt durch die histopathologische Befundung. Bone tumors of the heel are rare, soft tissue tumors are even less often. Nevertheless, a tumor should always be excluded as the cause of prolonged heel pain. Most of the tumors are benigne whereby calcaneus cysts are most common. Most common malignant tumors are osteosarcomas, chondrosarcomas and Ewing sarcomas. Some of the entities behave similarly to other skeleton regions, others show special characteristics on the foot. First line imaging is conventional X-rays under load. In most cases MRI examination and in some cases an additional CT scan should be supplemented. Histopathological examination is necessary to confirm the definitive diagnosis. 

Differentialdiagnose von Knochen- und Weichteiltumoren sowie tumorähnlichen Läsionen der Ferse

In this study, the impact of traditional rice-based fermented alcoholic beverages (Apong) on the gut microbiome and health of the Mishing community in India was examined. Two groups that consumed one of these beverages were compared to a control group that did not consume either beverage. Gut microbial composition was analyzed by sequencing 16S rRNA of fecal metagenomes and analyzing untargeted fecal metabolites, and short-chain fatty acids (SCFAs). We also collected data on anthropometric measures and serum biochemical markers. Our results showed that Apong drinkers had higher blood pressure, but lower blood glucose and total protein levels than other non-drinkers. Also, gut microbiome composition was found to be affected by the choice of Apong, with Apong drinkers having a more diverse and distinct microbiome compared to non-drinkers. Apong drink type or being a non-drinker explained even a higher variation of fecal metabolome composition than microbiome composition and Apong drinkers had lower levels of the SCFA isovaleric acid than non-drinkers. Overall, this study shows that a single dietary factor can significantly impact the gut microbiome of a community and highlights the potential role of traditional fermented beverages in maintaining gut health.

/pdf/a-single-dietary-factor-daily-consumption-of-a-fermented-2l8gphww.pdf

Falk Hildebrand

Papers

Erhebung der Forschungsstrukturen in der Unfallchirurgie

Glacier melt-down changes habitat characteristics and unique microbial community composition and physiology in Alpine lakes sediments.

Enrichment of gut microbiome strains for cultivation-free genome sequencing using droplet microfluidics

Differentialdiagnose von Knochen- und Weichteiltumoren sowie tumorähnlichen Läsionen der Ferse

A single dietary factor, daily consumption of a fermented beverage, can modulate the gut microbiome within the same ethnic community