The complexities of host–microbiota interaction

▸ Gevers D, Kugathasan S, Denson LA, et al. The treatment-naïve microbiome in new-onset Crohn's Disease. Cell Host Microbe 2014;15:382–92.

Crohn's disease is a complex disorder in which genetics and environmental factors establish and contribute to disease pathogenesis. Genetic studies implicate an underlying role for aberrant immune responses central to microbial sensing/signalling and mucosa-initiated effector responses. It is now well recognised that the gut microbiome plays an important role in disease pathogenesis but many current studies are confounded by size/power and treatment effects. To improve the understanding of the microbiota contribution to Crohn's disease pathogenesis, this study applied a standardised analysis approach to a large multi-centre cohort of new-onset Crohn's disease patient samples, collected prior to therapy. The study characterised mucosal-associated and faecal microbiota communities in Crohn's disease patients and a cohort of non-IBD patients. A total of 1321 samples including 630 ileal and 387 rectal tissue biopsies and 304 stool samples were subjected to microbial profiling using 16S rRNA gene sequencing, generating more than 45 million Illumina sequencing reads. Unweighted comparison of mucosal-associated microbiota from new-onset Crohn's disease and controls indicated that disease phenotype was not strong enough to differentiate patients. Biomarker detection analysis showed that inflammation was, as expected, strongly associated with a drop in species richness and an alteration in certain taxa abundance including Enterobacteriaceae, Bacteroidales and Clostridiales. Additionally, other taxa were identified as being positively correlated with Crohn's disease: Pasteurellaceae (Haemophilus sp), Veillonellaceae, Neisseriaceae and Fusobacteriaceae. Interestingly, the imbalance in microbial communities was only observed in mucosal samples and not seen in stool samples. The study further highlights the importance of defining the role of the microbiota in new-onset disease and also how essential it is to collect the correct sample type. The study provides a unique and unrivalled snapshot of treatment-naive Crohn's disease.

SIRT1/lipin-1 signalling as a therapeutic target in alcohol-induced liver disease

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