By conducting a multi-omic study of the microbiome, a multi-institutional research team acquired a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease (IBD). The researchers, participants in the second phase of the Human Microbiome Project, report that they have identified promising new targets for potential IBD treatments, including polyunsaturated fatty acids, bile acid derivatives, and human immune response pathways.
The new study, which was led by researchers from Harvard T.H. Chan School of Public Health and the Broad Institute of MIT and Harvard, demonstrates how new data, tools, and protocols may improve research on IBD and the microbiome. First, the new study obtained detailed measurements that made it easy to observe and confirm findings from previous studies, such as a reduction in overall gut ecological diversity and the gain and loss of specific “pro-” and “anti-inflammatory” microbes during disease.
More importantly, the suite of tools deployed for this study allowed researchers to determine the reasons for the changes. The results showed that during periods of disease activity, people with IBD had fewer microbially derived chemicals, which they speculated could be due to a combination of factors, including less beneficial microbial metabolism, poorer nutrient absorption, greater water or blood levels in the bowels, and more urgent bowel movements. These factors decreased the overall stability of the gut microbial ecosystem, leading to more episodes of improper immune responses and overreaction to the normal gut microbiome among IBD patients.
Detailed findings appeared May 29 in the journal Nature, in an article titled, “Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.” The article describes the collection of microbiome measurements—metagenomic, metatranscriptomic, metabolomic, and others—that correspond to active and non-active disease states. The findings showed that different forms of IBD—Crohn’s disease compared with ulcerative colitis, for instance—had different effects on the activity and composition of the microbiome.
“We followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens),” wrote the article’s authors. “We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum.
“Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation.”
The gut microbiome is a community of trillions of microbes, including bacteria, viruses, and fungi. Each person has a distinct microbiome, and research indicates that the microbiome plays an important role in numerous diseases, including IBD, which affects more than 3.5 million people worldwide and is growing in prevalence. IBD is a chronic disease that is marked by periods of remission followed by flare-ups in which the disease becomes active.
“Given how tightly connected the microbiome is with our health and wellbeing, our results shed some light on how we might avoid the problems that arise when this relationship goes awry, and how we might be better stewards of these life-long companions,” said Jason Lloyd-Price, who worked on the study while a research scientist at Harvard Chan School and the Broad Institute and was lead author of the paper.
“Our results from this study pave the way for early detection of upcoming flares in disease activity—which can then be aggressively treated—or potentially for new biochemical therapeutic opportunities to encourage complete remission of IBD,” added Curtis Huttenhower, PhD, professor of computational biology and bioinformatics at Harvard Chan School and associate member at the Broad Institute and senior author of the study.