Metabolic profiling and compound-class identification reveal alterations in serum triglyceride levels in mice immunized with human vaccine adjuvant Alum.

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Khoomrung S, Nookaew I, Sen P, Olafsdottir TA, Persson J, Moritz T, Andersen P, Harandi AM, Nielsen J.

J Proteome Res. 2019 Oct 18. doi: 10.1021/acs.jproteome.9b00517. PMID: 31625748

Abstract

Alum has been widely used as an adjuvant for human vaccines; however, the impact of Alum on host metabolism remains largely unknown. Herein, we applied mass spectrometry (LCMS)-based metabolic and lipid profiling to monitor the effects of Alum adjuvant on mouse serum at 6, 24, 72 and 168 h post-vaccination. We propose a new strategy termed Subclass Identification and Annotation for Metabolomics (SIAM) for class-wise identification of untargeted metabolomics data generated from high-resolution MS. Using this approach, we identified and validated the levels of several lipids in mouse serum that were significantly altered following Alum administration. These lipids showed a biphasic response even 168 h after vaccination. The majority of the lipids were triglycerides (TAGs), where TAGs with long chain unsaturated fatty acids were decreased at 24 h, and TAGs with short chain fatty acids were decreased at 168 h. To our knowledge, this is the first report on the impact of the human vaccine adjuvant Alum on host metabolome, and may provide new insights into the mechanism of action of Alum.

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An Assessment of Oxford Nanopore Sequencing for Human Gut Metagenome Profiling: A Pilot Study of Head and Neck Cancer Patients

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Thidathip Wongsurawat, Mayumi Nakagawa, Omar Atiq, Hannah N. Coleman, Piroon Jenjaroenpun, James I. Allred, Angela Trammel, Pantakan Puengrang, David W. Ussery, Intawat Nookaew

J Microbiol Methods. 2019 Oct 15:105739. doi: 10.1016/j.mimet.2019.105739. PMID: 31626891

Abstract

Gut metagenome profiling using the Oxford Nanopore Technology (ONT) sequencer was assessed in a pilot-sized study of 10 subjects. The taxonomic abundance of gut microbiota derived from ONT was comparable with Illumina Technology (IT) for the high-abundance species. IT better detected low-abundance species through amplification, when material was limited.

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ArC-GEM at Little Rock Tech Fest 2019!

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Big Data Comes to Biology: Portable Genome Sequencing

DNA sequencing will soon be possible from small mobile devices connected to a mobile phone. This workshop will demonstrate use of a hand-held sequencing device, that is about the same size as a Snicker’s candy bar. A brief overview of DNA sequencing will be discussed, along with some examples of high-throughput comparison of genome sequences. Personal genome sequencing from companies like 23andme and AncestoryDNA will be discussed, in the context of a general overview of current technologies and potential future applications.

Gastrointestinal tract dysbiosis enhances distal tumor progression through suppression of leukocyte trafficking

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Samir V. Jenkins,Michael S. Robeson II, Robert J. Griffin, Charles M. Quick, Eric R. Siegel, Martin J. Cannon, Kieng B. Vang, and Ruud P.M. Dings

Cancer Research, published online 7 October, 2019; DOI: 10.1158/0008-5472.CAN-18-4108.

Abstract

The overall use of antibiotics has increased significantly in recent years. Besides fighting infections, antibiotics also alter the gut microbiota. Commensal bacteria in the gastrointestinal tract are crucial to maintain immune homeostasis, and microbial imbalance or dysbiosis affects disease susceptibility and progression. We hypothesized that antibiotic-induced dysbiosis of the gut microbiota would suppress cytokine profiles in the host, thereby leading to changes in the tumor microenvironment. The induced dysbiosis was characterized by alterations in bacterial abundance, composition, and diversity in our animal models. On the host side, antibiotic-induced dysbiosis caused elongated small intestines and ceca, and B16-F10 melanoma and Lewis Lung carcinoma progressed more quickly than in control mice. Mechanistic studies revealed that this progression was mediated by suppressed TNF-α levels, both locally and systemically, resulting in reduced expression of tumor endothelial adhesion molecules, particularly intercellular adhesion molecule-1 (ICAM-1) and a subsequent decrease in the number of activated and effector CD8+ T-cells in the tumor. However, suppression of ICAM-1 or its binding site, the alpha subunit of lymphocyte function-associated antigen-1, was not seen in the spleen or thymus during dysbiosis. TNF-α supplementation in dysbiotic mice was able to increase ICAM-1 expression and leukocyte trafficking into the tumor. Overall, these results demonstrate the importance of commensal bacteria in supporting anticancer immune surveillance, define an important role of tumor endothelial cells within this process, and suggest adverse consequences of antibiotics on cancer development.

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