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The multifactorial aetiology of IBD
Lloyd-Price J, Arze C, Ananthakrishnanm AN, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 2019 569:655–662.
While it is recognised that IBD is the result of a complex interplay between host, environmental and microbial factors, the ability to perform integrative analyses to explore the multifactorial aetiology has been limited. To interrogate and develop a systems-level understanding, the Integrative Human Microbiome Project (HMP2) recruited and followed 132 participants (67 Crohn’s disease, 38 UC and 27 non-IBD) over 12 months and generated integrated longitudinal molecular profiles of their host and microbial activity. Overall, interindividual variation in microbiome profiles accounted for the majority of variance, outweighing relatively large effects including disease status. Metabolomic analysis highlighted differences between patients with IBD and non-IBD subjects, with less diverse metabolite profiles observed in patients with IBD. This parallels previous microbiota findings. No metagenomic signatures were shown to be predictive of disease status, which contrasts with previous studies, although there were differences in cohort selection which could explain the differing findings. Previously unobserved biochemical differences were detected during dysbiosis (not all limited to IBD-induced dysbiosis). Several acylcarnitines, which are microbially modified compounds, were significantly enriched in dysbiosis. One hundred and seventeen of 548 tested metabolites were significantly altered in dysbiosis in patients with IBD. By combining faecal and biopsy data sets and searching for both host and microbial molecular interactions, a large-scale cross-measurement type association network was constructed. This indicated that both Faecalibacterium prausnitzii and Escherichia coli are associated strongly with significant decreases and increases, respectively, in enzyme commission gene families. There was also a strong suggestion that Roseburia and Subdoligranulum species were involved in carnitine and bile acid dysregulation seen in IBD.
A novel model of non-alcoholic fatty liver disease (NAFLD)
Ouchi R, Togo S, Kimura M, et al. Modelling steatohepatitis in humans with pluripotent stem cell-derived organoids. …
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