Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

This study examined the dynamics of the cerebral blood flow response to hypoxia and hypercapnia in humans. Middle cerebral artery blood flow (MCAF) was assessed continuously using transcranial Doppler ultrasound. MCAF was calculated on a beat-by-beat basis as the product of the intensity-weighted mean velocity and the total power of the reflected signal. End-tidal PCO2 (PETCO2) and PO2 (PETO2) were controlled using a dynamic end-tidal forcing system. Six repeats of each of four protocols were administered to six subjects. The first was a control protocol with PETO2 held at 100 Torr and PETCO2 held 1-2 Torr above eucapnia throughout. The second was a hypoxic step protocol with PETO2 lowered from control values to 50 Torr for 20 min. The third was a hypercapnic step protocol with PETCO2 elevated from control by 7.5 Torr for 20 min. The fourth was a hypoxic-and-hypercapnic step protocol lasting 20 min. The total power of the Doppler signal remained relatively constant, suggesting that the cross-sectional area of the vessel changed little. After the initial transient in MCAF at the onset of the stimulus, no adaptation or progressive increase was observed over the remaining 20 min. A simple model consisting of a single pure delay, gain terms, time constants, and offsets for the on and off transients was fitted to the hypoxic and hypercapnic protocols. For hypercapnia, all the parameters for the onset were significantly different from the relief of the stimulus. The asymmetry was characterized by a slower on transient than off transient and also by a degree of undershoot after the relief of hypercapnia. Finally, the results from this study show that the cerebral blood flow response to hypoxia and hypercapnia in humans is much faster than has previously been thought.

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Completion of the Human Genome Project and the HapMap Project has led to increasing demands for mapping complex traits in humans to understand the aetiology of diseases. Identifying variations in the DNA sequence, which affect how we develop disease and respond to pathogens and drugs, is important for this purpose, but it is difficult to identify these variations in large sample sets. Here we show that through a combination of capillary sequencing and polymerase chain reaction assisted by gold nanoparticles, it is possible to identify several DNA variations that are associated with age-related macular degeneration and psoriasis on significant regions of human genomic DNA. Our method is accurate and promising for large-scale and high-throughput genetic analysis of susceptibility towards disease and drug resistance.