A 2020 clinical study showed that Gram-negative bacteria in the gut can cause cavernous angiomas in brain vessels. Cavernous angiomas are ballooning new capillaries developing from brain blood vessels. These arterial malformations of brain arteries occur in about 0.5% of the population. But according to this link only 40% of patients with cavernous angiomas become symptomatic. There are familial cases due to genetic causation. In these cases, often 5 or more lesions are identified on an MRI scan. Most cavernous angiomas occur in adults, but physicians found 25% of them in children. They can bleed, but do not bleed as much as arteriovenous malformations or aneurysms. Seizures are common in patients with cavernous angiomas. A new publication dated May 27, 2020 in Nature Communications compared 122 patients with cavernous angiomas to 27 controls who did not have cavernous angiomas on MRI brain scans.
Details of study in Nature Communications
All patients had stool examinations with a technique called “metagenomic shotgun sequencing analysis”. This is an advanced genomic analysis of stool samples. The authors could determine whether the gut bacteria were Gram-positive or Gram-negative. They also could identify the mix of various gut bacteria types. To their surprise there was a clear correlation between a mix of gram-negative bacteria of patients who had cavernous angiomas in their brain arteries versus controls who did not.
Many bacteria accumulate lipopolysaccharides. The genetic studies showed that cavernous angioma patients accumulated more bacteria in their large intestine that produce higher amounts of lipopolysaccharides.
Types of bacteria associated with higher risk of developing cavernous angioma
The researchers also determined that 5 Gram-negative gut bacteria were involved in causing cavernous angiomas (Bifidobacterium adolescentis, Bacteroides eggerthii, Bacteroides dorei, Dorea, and Escherichia coli). The researchers used information from MRI scans of the brain and genomic analysis of stool samples in the same patient. This way they could predict who was at a higher risk of bleeding from a cavernous angioma and who was not. When the bowel flora consisted of Gram-positive bacteria there was no risk of developing cavernous angiomas.
There were three types of Gram-positive gut bacteria that were particularly protective (F. prausnitzii, B. adolescentis and other Gram-positive species). When they were present in the gut flora, the gut was protected from inflammation. On the other hand, the Gram-negative species O. splanchnicus caused gut inflammation. Apart from causing cavernous angioma it has been implicated in causing other neurological disorders as well.
Plasma circulating factors
The researchers also identified certain plasma circulating factors that were present in patients who developed cavernous angioma and absent in non-cavernous angioma patients. The Gram-negative bacteria in the gut flora showed a close connection to these plasma circulating factors. The researchers postulated that they likely were the missing link why a certain gut flora constellation caused cavernous angiomas.
Gram-Negative Bacteria in the Gut Can Cause Cavernous Angiomas
Conclusion
A relatively rare arterial malformation of the brain, cavernous angioma, can cause brain hemorrhage, seizures and deterioration of mental functioning from scarring. A new study published in Nature Communications in May 2020 compared 122 patients with cavernous angiomas to 27 controls. Radiologists identified the lesions by MRI scans. The researchers analyzed stool bacteria in the same patients. For this they employed “metagenomic shotgun sequencing analysis”. This is an advanced genomic analysis of stool samples. The researchers were able to show that cases who developed cavernous angiomas had Gram-negative bacteria in their stools. Controls without cavernous angiomas had Gram-positive stool bacteria.
Plasma circulating factors may become a future blood test
In addition, the same patients who had Gram-negative stools had plasma circulating factors in their blood. Control patients did not have these plasma circulating factors. The researchers showed in other experiments that Gram-negative bacteria in the gut were causing gut inflammation, which caused the plasma circulating factors. They in turn are likely the cause of cavernous angiomas. The researchers think that further research of the plasma circulating factors will lead to a future blood test that can warn physicians of the risk of a cavernous angioma. Physicians may also consider bowel flora intervention with probiotics in the future to prevent cavernous angioma. This research confirms once again that a defective bowel flora can have serious consequences to human health.
