Reduction of trimethylamine N-oxide to trimethylamine by the human gut microbiota: supporting evidence for ‘metabolic retroversion’

Dietary sources of methylamines such as choline, trimethylamine (TMA), trimethylamine N-oxide (TMAO), phosphatidylcholine (PC) and carnitine are present in a number of foodstuffs, including meat, fish, nuts and eggs. It is recognized that the gut microbiota is able to convert choline to TMA in a fermentation-like process. Similarly, PC and carnitine are converted to TMA by the gut microbiota. It has been suggested that TMAO is subject to ‘metabolic retroversion’ in the gut (i.e. it is reduced to TMA by the gut microbiota, with this TMA being oxidized to produce TMAO in the liver). Sixty-six strains of human faecal and caecal bacteria were screened on solid and liquid media for their ability to utilize trimethylamine N-oxide (TMAO), with metabolites in spent media profiled by Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy. Enterobacteriaceae produced mostly TMA from TMAO, with caecal/small intestinal isolates of Escherichia coli producing more TMA than their faecal counterparts. Lactic acid bacteria (enterococci, streptococci, bifidobacteria) produced increased amounts of lactate when grown in the presence of TMAO, but did not produce large amounts of TMA from TMAO. The presence of TMAO in media increased the growth rate of Enterobacteriaceae; while it did not affect the growth rate of lactic acid bacteria, TMAO increased the biomass of these bacteria. The positive influence of TMAO on Enterobacteriaceae was confirmed in anaerobic, stirred, pH-controlled batch culture fermentation systems inoculated with human faeces, where this was the only bacterial population whose growth was significantly stimulated by the presence of TMAO in the medium. We hypothesize that dietary TMAO is used as an alternative electron acceptor by the gut microbiota in the small intestine/proximal colon, and contributes to microbial population dynamics upon its utilization and retroversion to TMA, prior to absorption and secondary conversion to TMAO by hepatic flavin-containing monooxygenases. Our findings support the idea that oral TMAO supplementation is a physiologically-stable microbiota-mediated strategy to deliver TMA at the gut barrier

Learning and interaction in groups with computers: when do ability and gender matter?

In the research reported in this paper, we attempt to identify the background and process factors influencing the effectiveness of groupwork with computers in terms of mathematics learning. The research used a multi-site case study design in six schools and involved eight groups of six mixed-sex, mixed-ability pupils (aged 9-12) undertaking three research tasks – two using Logo and one a database. Our findings suggest that, contrary to other recent research, the pupil characteristics of gender and ability have no direct influence on progress in group tasks with computers. However, status effects – pupils' perceptions of gender and ability – do have an effect on the functioning of the group, which in turn can impede progress for all pupils concerned

Succession of Bifidobacterium longum strains in response to the changing early-life nutritional environment reveals specific adaptations to distinct dietary substrates

Diet-microbe interactions play a crucial role in infant development and modulation of the early-life microbiota. The genus Bifidobacterium dominates the breast-fed infant gut, with strains of B. longum subsp. longum (B. longum) and B. longum subsp. infantis (B. infantis) particularly prevalent. Although transition from milk to a more diversified diet later in infancy initiates a shift to a more complex microbiome, specific strains of B. longum may persist in individual hosts for prolonged periods of time. Here, we sought to investigate the adaptation of B. longum to the changing infant diet. Genomic characterisation of 75 strains isolated from nine either exclusively breast- or formula-fed (pre-weaning) infants in their first 18 months revealed subspecies- and strain-specific intra-individual genomic diversity with respect to glycosyl hydrolase families and enzymes, which corresponded to different dietary stages. Complementary phenotypic growth studies indicated strain-specific differences in human milk oligosaccharide and plant carbohydrate utilisation profiles of isolates between and within individual infants, while proteomic profiling identified active polysaccharide utilisation loci involved in metabolism of selected carbohydrates. Our results indicate a strong link between infant diet and B. longum subspecies/strain genomic and carbohydrate utilisation diversity, which aligns with a changing nutritional environment: i.e. moving from breast milk to a solid food diet. These data provide additional insights into possible mechanisms responsible for the competitive advantage of this Bifidobacterium species and its long-term persistence in a single host and may contribute to rational development of new dietary therapies for this important developmental window

Succession of Bifidobacterium longum strains in response to a changing early life nutritional environment reveals dietary substrate adaptations

Diet-microbe interactions play a crucial role in modulation of the early life microbiota and infant health. Bifidobacterium dominates the breast-fed infant gut and may persist in individuals during transition from a milk-based to a more diversified diet. Here, we investigated adaptation of B. longum to the changing nutritional environment. Genomic characterisation of 75 strains isolated from nine either exclusively breast- or formula-fed (pre-weaning) infants in their first 18 months revealed subspecies- and strain-specific intra-individual genomic diversity with respect to carbohydrate metabolism, which corresponded to different dietary stages. Complementary phenotypic studies indicated strain-specific differences in utilisation of human milk oligosaccharides and plant carbohydrates, while proteomic profiling identified gene clusters involved in metabolism of selected carbohydrates. Our results indicate a strong link between infant diet and B. longum diversity and provide additional insights into possible competitive advantage mechanisms of this Bifidobacterium species and its persistence in a single host

Scaling in Complex Systems: Analytical Theory of Charged Pores

In this paper we find an analytical solution of the equilibrium ion distribution for a toroidal model of a ionic channel, using the Perfect Screening Theorem (PST). The ions are charged hard spheres, and are treated using a variational Mean Spherical Approximation (VMSA) . Understanding ion channels is still a very open problem, because of the many exquisite tuning details of real life channels. It is clear that the electric field plays a major role in the channel behaviour, and for that reason there has been a lot of work on simple models that are able to provide workable theories. Recently a number of interesting papers have appeared that discuss models in which the effect of the geometry, excluded volume and non-linear behaviour is considered. We present here a 3D model of ionic channels which consists of a charged, deformable torus with a circular or elliptical cross section, which can be flat or vertical (close to a cylinder). Extensive comparisons to MC simulations were performed. The new solution opens new possibilities, such as studying flexible pores, and water phase transformations inside the pores using an approach similar to that used on flat crystal surfaces

The complex process of scaling the integration of technology enhanced learning in mainstream classrooms

The early optimism for how technology might transform teaching and learning practices in mainstream school classrooms has long faded in many countries around the world. Whilst early research findings suggested that this was due to obvious barriers such as access to the technology itself, more recent attempts to scale student-access have illuminated other factors and provided a more sound theoretical foundation for us to understanding the processes and products of scaling educational technology innovations. This keynote will use findings from key projects and initiatives to highlight what is being learned – and how this might inform future endeavours to realise a more 21st century curriculum

Rethinking the discovery function of proof within the context of proofs and refutations

Proof and proving are important components of school mathematics and have multiple functions in mathematical practice. Among these functions of proof, this paper focuses on the discovery function that refers to invention of a new statement or conjecture by reflecting on or utilizing a constructed proof. Based on two cases in which eighth and ninth graders engaged in proofs and refutations, we demonstrate that facing a counterexample of a primitive statement can become a starting point of students’ activity for discovery, and that a proof of the primitive statement can function as a useful tool for inventing a new conjecture that holds for the counterexample. An implication for developing tasks by which students can experience this discovery function is mentioned.ArticleInternational Journal of Mathematical Education in Science and Technology. 45(7):1053-1067 (2014)journal articl

IMP: Imperial Metagenomics Pipeline for high-throughput sequence data

We have developed an in-house pipeline for the processing and analyses of sequence data generated during Illumina technology-based metagenomic studies of the human gut microbiota. Each component of the pipeline has been selected following comparative analysis of available tools; however, the modular nature of software facilitates replacement of any individual component with an alternative should a better tool become available in due course. The pipeline consists of quality analysis and trimming followed by taxonomic filtering of sequence data allowing reads associated with samples to be binned according to whether they represent human, prokaryotic (bacterial/archaeal), viral, parasite, fungal or plant DNA. Viral, parasite, fungal and plant DNA can be assigned to species level on a presence/absence basis, allowing – for example – identification of dietary intake of plant-based foodstuffs and their derivatives. Prokaryotic DNA is subject to taxonomic and functional analyses, with assignment to taxonomic hierarchies (kingdom, class, order, family, genus, species, strain/subspecies) and abundance determination. After de novo assembly of sequence reads, genes within samples are predicted and used to build a non-redundant catalogue of genes. From this catalogue, per-sample gene abundance can be determined after normalization of data based on gene length. Functional annotation of genes is achieved through mapping of gene clusters against KEGG proteins, and InterProScan. The pipeline is undergoing validation using the human faecal metagenomic data of Qin et al. (2014, Nature 513, 59–64). Outputs from the pipeline allow development of tools for the integration of metagenomic and metabolomic data, moving metagenomic studies beyond determination of gene richness and representation towards microbial-metabolite mapping. There is scope to improve the outputs from viral, parasite, fungal and plant DNA analyses, depending on the depth of sequencing associated with samples. The pipeline can easily be adapted for the analyses of environmental and non-human animal samples, and for use with data generated via non-Illumina sequencing platforms