Steady-State Microbiome and Metabolome

The Byrd Lab studies how the gut microbiome and its metabolic products — known as the metabolome — shape human health. Alongside research in patients with cancer or autoimmune diseases, the lab analyzes samples from healthy volunteers to understand what drives microbiome and metabolome composition in a stable, “steady-state” condition.

To support this work, the lab collaborated with the Institut Pasteur’s Milieu Intérieur consortium to create a comprehensive dataset of 1,359 gut microbiome samples from 946 healthy donors (Byrd et al., Journal of Experimental Medicine, 2021). Using a novel reference database, the team found age and biological sex were the strongest factors shaping microbial communities, underscoring why these variables matter in microbiome research.

This healthy baseline allowed the lab to detect global shifts in the gut microbiomes of patients with non-gastrointestinal cancers. While microbial imbalances had been well documented in colorectal cancer, this study revealed, for the first time, that patients with other types of cancer also exhibit altered microbial communities compared with age-matched healthy donors. Specifically, these patients had reduced bacterial diversity and increased levels of Bacteroides species. The lab continues to use this baseline to compare healthy and disease-associated microbial profiles, advancing understanding of how microbial changes influence health and disease.

Building on these findings, the lab is now expanding into metabolomics. Gut microbes produce and modify a wide array of metabolites, which can influence immune activation and tissue function. Imbalances in gut microbes, common in autoimmune disease, may affect immune responses by altering the body’s metabolite patterns. By mapping these microbial and metabolic profiles, the Byrd Lab seeks insights that could lead to new ways to prevent or treat immune system diseases.