Of the thousands of species of bacteria that live in the digestive tract, scientists know only a handful of them directly influence human health.
In a new study, researchers have discovered a group of gut bacteria that can metabolize enough cholesterol to potentially affect people’s heart health.
They found that people who have these bacteria in their intestines have lower cholesterol levels in their blood than those without the microbes.
The discovery suggests a possible reason why some people can consume more cholesterol in their diet with minimal effect on their blood cholesterol levels.
It also hints that boosting populations of these bacteria, through diet, probiotics, or another kind of treatment, may one day be an effective way to help lower cholesterol levels.
The research was conducted by a team at the Broad Institute of MIT and Harvard University
The idea that bacteria can metabolize cholesterol isn’t a new one; in the early 1900s, scientists reported the existence of bacteria that could chemically transform cholesterol into a compound called coprostanol.
Coprostanol-generating bacteria have been found in the guts of rats, baboons, pigs, and even humans, but the biology of these bacteria was poorly understood.
It’s been known for a long time that some gut bacteria could form coprostanol from cholesterol, but researchers didn’t know which species of bacteria were doing this or how they were doing it.
In the study, the team wanted to know whether there was a link between these bacteria and blood cholesterol levels.
But isolating cholesterol-metabolizing bacteria and growing them in the lab proved to be difficult—many species found in the human microbiome are hard to culture in the lab.
Instead, the team turned to large microbiome datasets to unearth genes that might be involved in cholesterol metabolism.
The researchers analyzed gut microbiomes from 3,097 people across the United States and sequenced nearly 6 million microbial genes found in those microbiomes.
Of the microbiome samples, 625 also included information on levels of coprostanol found in the feces.
The team looked for bacterial genes that were present only in people who excreted coprostanol and also resembled those encoding enzymes that perform similar functions to cholesterol metabolism.
That led the scientists to just four genes that might be involved in breaking down cholesterol.
From there, the researchers genetically engineered bacteria in the lab to produce each of the four enzymes of interest.
They homed in on one gene, which they named Intestinal Stool Metabolism A (IsmA), that could metabolize cholesterol. The gene, they showed in their genetic data, is found in a small number of microbiome-associated bacteria.
The group discovered that people with the IsmA gene in their microbiome excreted 55-75% less cholesterol in their feces than people who don’t carry that bacterial gene.
Moreover, people with the IsmA gene had, on average, cholesterol levels in the blood that was 0.15 mmol/L (2.7 mg/dL) lower than those without any copies of the IsmA genes in their microbiomes.
This is a larger average effect on blood cholesterol than human genes such as HMGCR and PCSK9, which are known to alter a person’s risk of high cholesterol levels and are targeted by some FDA-approved cholesterol drugs.
The researchers are now trying to isolate the human-associated bacteria that carry IsmA for further study, and have additional questions about whether coprostanol has any effect on human health.
But they say their results validate the idea that the makeup of a person’s microbiome can impact their metabolic health.
One author of the study is Ramnik Xavier, the director of Broad’s Immunology Program.
The study is published in Cell Host and Microbe.
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