June 16, 2020

Gut bacteria may contribute to abnormal blood vessel formation

At a Glance

  • People with abnormal clusters of blood vessels in the brain called cavernous angiomas had differences in their gut bacteria compared to people without the condition.
  • The findings could help lead to development of new diagnostic tests and treatments.
Cavernous angioma on brain scan The study found a link between the appearance of abnormal blood vessel bundles called cavernous angiomas and the composition of a person’s gut bacteria. Awad lab, University of Chicago

The walls of the blood vessels need to be strong and springy to handle the pressure needed to pump blood from the heart through the body. But in a condition called cavernous angioma (CA), bundles of brittle, fragile blood vessels form in the brain, spinal cord, or both.

Blood can stagnate in these fragile bundles, also called cerebral cavernous malformations, and leak into the brain. This can lead to headaches, seizures, or brain hemorrhages. Medications can lessen these symptoms, but the primary treatment for CA is surgical removal.

Several genetic variations have been linked to the development of CA. Such variations can be inherited or occur spontaneously. But the presence of these gene variations is not enough to predict who will develop severe, symptomatic CA. Recent research in mice has suggested that the composition of the microbiome may also influence CA severity. The microbiome comprises the bacteria, viruses, and fungi that normally live in the gut, skin, and elsewhere in the body.

Previous work from a research team led by Drs. Le Shen and Issam Awad from the University of Chicago found changes in the microbiome among a small group of people with CA. To more closely explore how the gut microbiome might influence CA formation, the team enrolled 122 people with at least one CA identified by imaging scans into a new study.

The researchers used gene sequencing techniques to identify the bacterial species and their relative abundance in participants’ stool. They then compared these bacterial signatures to age- and sex-matched participants in a different study who didn’t have CA.

The study was funded in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS), National Heart, Lung, and Blood Institute (NHLBI), and National Center for Advancing Translational Sciences (NCATS). Results were published on May 27, 2020, in Nature Communications.

The team found differences between people with and without CA in the overall diversity of bacterial species and in levels of specific species. These differences were seen regardless of the geographic location of the participants, age, sex, or whether the disease mutations were inherited or spontaneous. A test that measured the levels of just three species was more than 90% accurate at identifying which people in the study had CA.

People with CA harbored more types of bacteria that produce molecules called lipopolysaccharides (LPS) and also had significantly different levels of LPS in their blood. These results are consistent with the previous discovery in mice of an interaction between LPS produced by bacteria and the cells lining CA blood vessels.

Further analysis showed that some gut bacteria compositions could identify aggressive versus non-aggressive forms of the disease, as well as people with recent symptomatic hemorrhages. Notably, bacteria known to protect against inflammation were reduced in people with CA. By combining microbiome signatures with measures of inflammatory molecules in blood, the team was able to further improve predictions of disease severity.

This approach could potentially be used to predict the risk of complications from CA. However, more research is needed to test how the microbiome might be used to make diagnoses and predict prognoses.

“Future studies are needed to see if modifying the microbiome, through diet or other means, has the potential to reduce bleeding and other symptoms of the disorder,” Awad says.

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References: Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma. Polster SP, Sharma A, Tanes C, Tang AT, Mericko P, Cao Y, Carrión-Penagos J, Girard R, Koskimäki J, Zhang D, Stadnik A, Romanos SG, Lyne SB, Shenkar R, Yan K, Lee C, Akers A, Morrison L, Robinson M, Zafar A, Bittinger K, Kim H, Gilbert JA, Kahn ML, Shen L, Awad IA. Nat Commun. 2020 May 27;11(1):2659. doi: 10.1038/s41467-020-16436-w. PMID: 32461638.

Funding: NIH’s National Institute of Neurological Disorders and Stroke (NINDS), National Heart, Lung, and Blood Institute (NHLBI), and National Center for Advancing Translational Sciences (NCATS); Department of Defense; BeBrave for Life Foundation; University of Chicago; American Association of Neurological Surgeons/Congress of Neurological Surgeons; Sigrid Juselius Foundation; William and Judith Davis Fund in Neurovascular Surgery Research.