Researchers from the Institute of Systems Biology in Seattle report a striking split in what shapes the blood metabolome: gut bacteria drive the majority of detectable substances, while genetics account for a smaller portion. The study, published in Nature Metabolism, found that about 69% of blood metabolites are linked to the activity of intestinal microbiota, with genetics responsible for roughly 15%. A combined 16% are influenced by both the host genome and the gut microbes.
To reach these conclusions, the team analyzed the blood metabolomes of more than 1,500 participants. They pinpointed which molecules are primarily controlled by microbial action and which are largely governed by genetic factors. This distinction matters because metabolites tied to gut bacteria tend to respond more readily to changes in diet, lifestyle, or medical treatment, offering potential routes to influence health through non-genetic means.
In addition to sequencing the participants’ DNA, researchers collected stool samples to characterize the gut microbiota. The results reinforced the main finding: the majority of metabolite associations stem from the gut microbiome alone, a smaller portion from genetics alone, and a remaining share from the joint effects of both systems. This multi-omics approach helps map how distant processes intersect at the level of circulating molecules.
Among the metabolites tied to genetic control, levels of bile acids and free fatty acids stood out, along with other molecules that have been linked to an elevated risk of late-onset Alzheimer’s disease. Conversely, the metabolites most strongly connected to gut microbial activity were involved in the microbial metabolism of aromatic and phenolic compounds, highlighting how bacteria can shape chemical signals in the bloodstream that influence health and disease risk.
The study demonstrates a clear path to modulating the blood metabolome by shaping the gut microbiome through diet, probiotics, or targeted therapies. It marks an important early step in a broader effort to map how circulating metabolites reflect the interplay between human biology and microbial inhabitants. While the findings are promising, researchers emphasize that more work is needed to translate these associations into actionable clinical strategies and to understand the long-term consequences of altering microbial ecosystems on systemic metabolism.
Overall, the work underscores the central role of the gut microbiome in systemic metabolism and invites ongoing exploration of how microbial communities may be harnessed to improve metabolic health in diverse populations across North America.