Nat Metab: The gut microbiome plays a huge role in shaping the molecules in our blood

The nearly 200-year-old phrase "what to eat like what" has new evidence
.
ISB researchers found that the gut microbiome, including the food we feed, largely influences changes in people's circulating blood metabolites
.
This knowledge will help guide targeted interventions
aimed at altering the composition of human blood metabolomes.

"We know that the differences between people on the blood metabolome — the small molecules found in the blood that can interact with all of our body's systems — can tell us a lot about health and disease states
.
Figuring out what controls this change is a necessary step to bring us closer to a precise approach to health care," said Sean Gibbons, Ph.
D.
, a faculty member at ISB and co-corresponding author
of the paper.

The team examined 930 blood metabolites
in more than 1500 human bodies.
More than 60% of the detected metabolites were significantly associated
with host genetics or the gut microbiome.
"Notably, 69 percent of these associations were driven entirely by the microbiome, 15 percent entirely by genetics, and 16 percent under the control of genetic-microbiome mixture," said Dr.
Christian Diener, senior research scientist at ISB and lead author
of the study.
Diener and co-first author Chengzhen Dai analyzed de-identified metabolome, genomic and microbiome data
from voluntary patients in the Consumer Science Health Program.

They found that changes in blood metabolites explained by the microbiome were largely independent of changes explained by the genome, even for hybrid metabolites that are significantly associated with both genetics and microbes
.
In addition, certain metabolite-microbe associations were only significant in individuals with specific genetic backgrounds, suggesting subtle interactions
between microbiome and host genetics in shaping the blood metabolome.

These new findings are promising for several
reasons.
First, a large number of microbio-specific metabolites suggest that our blood metabolome can be modified
by diet, probiotics, and other lifestyle interventions.
Second, metabolites under stricter gene control may not respond to lifestyle changes, making them targets
for pharmacological interventions that directly target host pathways.

Dr Andrew Magis, co-corresponding author of the paper, said: "A deeper understanding of the determinants of blood metabolome will provide us with a window into how these circulating metabolite levels are designed and optimized to promote health
.
Understanding which circulating small molecules are primarily controlled by the host and microbiome will help guide interventions
aimed at preventing and/or treating a range of diseases.
”

Diener, C.
, Dai, C.
L.
, Wilmanski, T.
et al.
Genome– microbiome interplay provides insight into the determinants of the human blood metabolome.
Nat Metab, 2022