Study finds hemorrhagic brain disease caused by gut bacteria metabolite
A milestone study published in the journal Nature Communications is offering the first demonstration of a direct causal relationship between the gut microbiome and a human neurovascular disease. Verifying prior animal studies, the research suggests a microbiome metabolite can travel through the bloodstream, reach blood vessels in the brain and expedite the development of lesions.
Cavernous angioma (CA) is a neurovascular disorder where strokes or seizures can be triggered by blood vessel abnormalities. The condition can be either inherited or sporadic, but it is still unclear exactly what other factors influence the severity and natural course of the disease.
Recent animal studies have pointed to a possible gut microbiome connection, with mouse studies revealing metabolites produced by specific gut bacteria can influence brain lesion volume. Of course, animal studies don’t mean a great deal unless they can be validated in human subjects.
"The implications of that [animal study] were very big," says Issam Awad, who worked on the earlier animal research and is senior author on the new study. "But we didn't know if this concept of a unique microbiome that favors the development of lesions would be true in human beings."
The researchers collected fecal samples from over 100 CA patients and discovered the condition did correlate with a very particular microbiome signature. Levels of three common species particularly distinguished CA patients from a healthy control. Higher than normal levels of Odoribacter splanchnicus were seen in CA patients, alongside lower levels of Faecalibacterium prausnitzii and Bifidobacterium adolescentis.
"The CA patients from all the different collection sites had the same distinctive microbiome, regardless of whether they had inherited the mutation or had a sporadic lesion, and regardless of the number of lesions they had," explains Awad.
Further analysis revealed the specific CA-microbiome signature identified in the human subjects resulted in heightened synthesis of lipopolysaccharide (LPS) molecules. Prior mouse studies have found LPS molecules produced in the gut can travel through the bloodstream into the brain and drive the development of CA lesions.
Sean Polster, first author on the new study, says analyzing microbial populations in tandem with a number of blood-based biomarkers resulted in incredibly accurate diagnoses of CA severity.
"By looking at both bacteria combinations and the blood biomarkers, we were able to measure just how aggressive the disease was in each patient," adds Polster.
Moving forward, the researchers are hesitant to suggest some kind of probiotic treatment could be effective in managing this kind of neurovascular disease. Awad particularly notes, the broader systemic effects of the gut microbiome can be unpredictable, so trying to alter levels of one or two types of bacteria could lead to other kinds of health problems. The microbiome, “is more complicated than it appears,” adds Awad.
The new study was published in the journal Nature Communications.