Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, affect millions of people worldwide. IBD profiles can vary greatly, making it a difficult disease to treat effectively.
In a new study, researchers from Harvard T.H. Chan School of Public Health and the Broad Institute of MIT and Harvard have catalogued the complex set of chemical and molecular events that disrupt the microbiome and trigger immune responses during flare ups of IBD. This multi-omics approach provides a deeper understanding with the microbial changes and genetic shifts involved in the disease and could inform development of future therapies. Their findings are published in Nature.
The study is part of the Human Microbiome Project, which launched in 2007.
The study followed 132 participants, some with IBD and others non-IBD controls, over a year-long period. Samples were taken periodically over the year, with a total of 651 biopsies and 529 blood samples collected in the clinic, and an additional 1,785 stool samples collected every two weeks using a home shipment protocol. Metagenomes, metatranscriptomes, proteomes, metabolomes, and viromes were generated for each participant were generated at several global timepoints from the stool samples. Biopsies yielded additional genomic sequencing data, which were matched with blood sequencing profiles. All data is available at https://ibdmdb.org/.
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This wealth of information allowed the researchers to confirm findings from previous studies, such as reduction in overall gut ecological diversity and gains of certain microbes during disease. On top of that, they were able to determine the reasons for the changes. During times of disease activity, people with IBD were observed to have fewer microbially-derived chemicals, perhaps due to a less beneficial microbial metabolism, poorer nutrient absorption, or other factors. Such factors could decrease overall stability in the gut microbial ecosystem and lead to more episodes of improper immune responses.
These findings provide the most detailed look to date of the microbiome in people with IBD. They found that different forms of IBD had different effects on activity and composition of the microbiome. These could lead to better ability for early detection of IBD symptoms and development and deployment of treatments for the disease.