Multi-omics of the Gut Microbial Ecosystem in Inflammatory Bowel Diseases

By Dr. Katie E. Golden, MD

Inflammatory Bowel Disease (IBD), which includes both Crohn’s disease and Ulcerative Colitis, has presented a number of challenges for scientists and clinicians who search for better treatment options for the increasing number of patients who suffer from the disease each year. We are just beginning to appreciate the complicated variation in genetic, immunological, and microbial factors that contribute to the development and progression of disease. As our understanding of this complex pathophysiology advances, there is a renewed emphasis on the need for broad data collection and analysis that will help us better capture and characterize the heterogeneous nature of IBD.

In a recently published paper in Nature, Lloyd-Price ( provide a comprehensive analysis of the longitudinal variation in the gut microbiome of patients with IBD.1   At its core, we know that IBD is a disease of dysbiosis, and that the microbiomes of IBD patients show significant variations from not only healthy controls, but also in the same individual in times of more severe clinical disease. In this study, researchers followed 132 patients over the course of a year to generate molecular profiles of host and microbial activity during disease course. They collected blood samples, stool samples, and intestinal tissue biopsies frequently throughout the length of the study, and analyzed their samples with metagenomic sequencing, metatranscriptomics, and metabolomics. Their data reveals a catalogue of new relationships between multi-omic features in IBD.

This large-scale analysis yielded several important findings. First, there was a characteristic increase in facultative anaerobes and decline in obligate anaerobes in the microbiomes of IBD subjects (suggested by previous research). With their advanced technology, however, researchers were able to describe disruptions in microbial transcription activity and metabolite abundance during disease activity. The authors found, for example, increased gene expression in clostridia species in periods of increased disease activity through metatranscriptome analysis. They also found characteric metabolite pool depletion in IBD patients; short-chain fatty acids and acylcarnitines were significantly reduced (and primary bile acids increased) during times of dysbiosis. Overall, the authors observed increased temporal variability in microbial communities of IBD subjects that correlated with periods of clinical disease. While these are just a few examples, collectively their data lays important groundwork for a number of novel host and microbial features that deserve further characterization as potential contributors to IBD.

1. Lloyd-Price, J. et al. Nature volume 569, 655–662 (2019)