NIH features early progress in understanding microbiome’s role in IBD

On Wednesday, Curtis Huttenhower, PhD, of the T.H. Chan Harvard School of Public Health and Broad Institute, shared some preliminary results from the Inflammatory Bowel Disease Multi’omics Database (IBDMDB), part of the Human Microbiome Project aiming to provide an integrated resource for characterizing the gut microbiota as it relates to IBD diagnosis and therapies. IBD “is of course … both a critical health condition in and of itself, and has become a really interesting model for the complex involvement.

IBD “is of course … both a critical health condition in and of itself, and has become a really interesting model for the complex involvement of the gut microbiome specifically in chronic disease,” Huttenhower said during his presentation. “Over about the past 5 to 10 years now, some better studies of the microbiome have helped to very quickly refine our understanding of this involvement from a high-level observation of ecological disruptions, reductions in diversity in the gut community during IBD, down to a much better understanding of specific taxa and their common metabolic and other molecular functions that are disrupted in subsets of IBD.”

IBDMDB researchers followed more than 100 individuals for 1 year, including patients with Crohn’s disease or ulcerative colitis and controls, and analyzed more than 4,000 stool, biopsy and blood samples to develop molecular profiles of host and microbial activity during IBD.

Highlighting some pilot studies within this project, Huttenhower said IBDMDB investigators identified microbially-processed small molecules implicated in IBD inflammation and severity by integrating microbial profiles with metabolomics. Additionally, they were able to pinpoint uniquely expressed microbes and pathways in a subset of patients with active disease.

IBDMDB “data represent a substantial community resource for future multi’omics studies in IBD, and have also served to provide the first integrated molecular profile of immune activity and clinical response during disease progression,” he and colleagues wrote.

Long-term goals of this research include better understanding the mechanisms driving dysbiosis in IBD, “what’s causal vs. responsive in the microbiome during IBD, changes in disease activity, and … helping to translate some of the emerging ecological understanding of the microbiome’s involvement into activities that would help in the clinic,” Huttenhower said. “This might involve for example, understanding the heterogeneity of the disease, … helping to predict response to treatment over time, predicting either the onset or remission of flares and disease activity, … and then identifying either on the host or microbial side, pathways, molecular targets that might be either causal or points of intervention for new treatments.”

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