1 r e s o u r c eChanges in the composition of the human gut microbiota have been associated with the development of chronic diseases including type 2 diabetes, obesity, and colorectal cancer 1 . Gut bacterial functions, such as synthesis of amino acids and vitamins 2 , breakdown of indigestible plant polysaccharides 3 , and production of metabolites involved in energy metabolism 4 , have been linked to human health. The use of 'omics approaches to study human microbiome communities has led to the generation of enormous data sets whose interpretations require systems biology tools to shed light on the functional capacity of gut microbiomes and their interactions with the human host 5 .In order to infer the metabolic repertoire of a gut metagenome data set, researchers usually map sequenced genes or organisms onto metabolic networks derived from the Kyoto Encyclopedia of Genes and Genomes (KEGG) 6 , and functional annotations from KEGG ontologies 7 . However, this approach cannot identify the contribution of each bacterial species to the metabolic repertoire of the whole gut microbiome, nor can it infer the effects of different gut microbial communities on host metabolism.A technique that can bridge this gap is constraint-based reconstruction and analysis (COBRA) 8 using genome-scale metabolic reconstructions (GENREs) of individual human gut microbes. GENREs are assembled using the genome sequence and experimental information 9 . These reconstructions form the basis for the development of condition-specific metabolic models whose functions are simulated and validated by comparison with experimental results. The models can be used to investigate genotype-phenotype relationships 10 , microbe-microbe interactions 11 , and host-microbe interactions 11 . Numerous tools can be used to automatically generate draft GENREs but such models contain errors 12 and are incomplete.Manual curation of draft reconstructions is time consuming because it involves an extensive literature review and experimental validation of metabolic functions 9 .To provide an extensive resource of GENREs for human gut microbes, we developed a comparative metabolic reconstruction method that enables any refinement to one metabolic reconstruction to be propagated to others. This accelerates reconstruction and improves model quality. We generated AGORA, which includes 773 gut microbes, comprising 205 genera and 605 species. All reconstructions were based on literature-derived experimental data and comparative genomics. The metabolic predictions of two AGORA reconstructions and their derived metabolic models were validated against experimental data. RESULTS Metabolic reconstruction pipelineWe devised a comparative metabolic reconstruction method (Fig. 1a,c), which is analogous to the comparative microbial genome annotation approach 13 that has enabled accelerated annotation by propagation of refinements to one genome to others. First, we downloaded draft GENREs using Model SEED 14 and KBase (US Department of Energy Systems Biology Knowledgebase, http:/...

Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely used animal models exhibit limitations. Here we present a modular, microfluidics-based model (HuMiX, human–microbial crosstalk), which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal human–microbe interface. We demonstrate the ability of HuMiX to recapitulate in vivo transcriptional, metabolic and immunological responses in human intestinal epithelial cells following their co-culture with the commensal Lactobacillus rhamnosus GG (LGG) grown under anaerobic conditions. In addition, we show that the co-culture of human epithelial cells with the obligate anaerobe Bacteroides caccae and LGG results in a transcriptional response, which is distinct from that of a co-culture solely comprising LGG. HuMiX facilitates investigations of host–microbe molecular interactions and provides insights into a range of fundamental research questions linking the gastrointestinal microbiome to human health and disease.

Nanocrystalline hydroxyapatite (HAp) prepared by a precipitation route was investigated. The X-ray diffraction (XRD) powder patterns of the elongated nanocrystals with a typical diameter of about 10 nm and length of 30-50 nm (by transmission electron microscopy (TEM)) revealed the presence of HAp with significantly broadened XRD reflections. However, Ca deficiency was found, as the Ca/P ratio was 1.5 only (so-called calcium-deficient hydroxyapatite (CDHA)), and not 1.67. This Ca deficiency of nanocrystalline HAp is explained using NMR. It is shown unambiguously that (i) the nanocrystals consist of a crystalline core and a (disordered) surface region with a relative phosphate content of about 1:1, (ii) the crystalline core is HAp, and (iii) the surface region is dominated by hydrogen phosphate anions (with no hydroxyapatite-like structural motif) and structural water (hydrate). From the relative phosphate content and taking into account the crystal shape, the thickness of the surface layer along the main crystal axis could be estimated to be about 1 nm, and the average chemical composition of the surface layer has been determined. Finally, a Ca/P ratio of 1.52 was estimated from the NMR data that compares well with the value of 1.51 from chemical analysis. The important consequences are that the surface of nanocrystalline HAp has nothing in common with the bulk composition and that the chemistry of such materials (e.g. the binding of protein molecules to phosphate surfaces) must be reconsidered.

Structuring over many length scales is a design strategy widely used in Nature to create materials with unique functional properties. We here present a comprehensive analysis of an adult sea urchin spine, and in revealing a complex, hierarchical structure, show how Nature fabricates a material which diffracts as a single crystal of calcite and yet fractures as a glassy material. Each spine comprises a highly oriented array of Mg-calcite nanocrystals in which amorphous regions and macromolecules are embedded. It is postulated that this mesocrystalline structure forms via the crystallization of a dense array of amorphous calcium carbonate (ACC) precursor particles. A residual surface layer of ACC and/or macromolecules remains around the nanoparticle units which creates the mesocrystal structure and contributes to the conchoidal fracture behavior. Nature’s demonstration of how crystallization of an amorphous precursor phase can create a crystalline material with remarkable properties therefore provides inspiration for a novel approach to the design and synthesis of synthetic composite materials.

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