Life science
Medical & healthcare, Drug development

Dysbiosis of gut microbiome is associated with rupture ofcerebral aneurysm
Department of Neurosurgery, Graduate School of Medicine
Assistant Professor Masatoshi Takagaki

https://researchmap.jp/osakansmt

Professor Haruhiko Kishima

https://researchmap.jp/hkishima

Life science

Abstract
The relationship between the gut microbiome and aneurysm rupture is unclear. We compared the gut microbiome in patients withunruptured intracranial aneurysms (UIAs) and ruptured aneurysms(RAs) to identify the specific bacteria causing the rupture of CAs.
Their gut microbiomes were analyzed using 16S rRNA sequencing. Subsequently, PCR was performed to identify the specificspecies. The gut microbiome in the RA and UIA groups exhibited
significantly different taxonomies. The abundance of the genus
Campylobacter and Campylobacter ureolyticus was significantly
higher in the RA group. The gut microbiome profile of patientswith stable UIAs and RAs were significantly different. The genus
Campylobacter and Campylobacter ureolyticus may be associatedwith the rupture of CAs.

▍ Significance of the research and Future perspective
The gut microbiome profile of patients with stable UIAs andRAs were significantly different. The genus Campylobacter andCampylobacter ureolyticus may be associated with the ruptureof CAs. With the results of this study, we expect that adding gut
microbiota as a new factor will allow us to predict the rupture of unruptured cerebral aneurysms with higher accuracy. In addition, webelieve that this will lead to a new treatment for unruptured cerebral
aneurysms by manipulating the gut microbiota.

▍ Background & Results
Background
Environmental factors are important with respect to the rupture ofcerebral aneurysms (CAs). However, the relationship between thegut microbiome, an environmental factor, and aneurysm rupture isunclear. Therefore, we compared the gut microbiome in patientswith unruptured intracranial aneurysms (UIAs) and ruptured aneurysms (RAs) to identify the specific bacteria causing the rupture ofCAs.
Methods
A multicenter, prospective case-control study was conducted
over one year from 2019 to 2020. The fecal samples of patientswith stable UIAs and RAs immediately aftetr onset were collected.
Their gut microbiomes were analyzed using 16S rRNA sequencing.
Subsequently, a phylogenetic tree was constructed and PCR wasperformed to identify the specific species.
Results
A total of 28 RAs and 33 UIAs were included in this study. There
was no difference in patient characteristics between RAs andUIAs: age, sex, hypertension, dyslipidemia, diabetes status, BMI,and smoking. No difference was observed in alpha diversity; however, beta diversity was significantly different in the unweighted
UniFrac distances. At the phylum level, the relative abundanceof Campylobacter in the RA group was larger than that in theUIA group. Furthermore, the gut microbiome in the RA and UIAgroups exhibited significantly different taxonomies. However,Campylobacter was focused on because it is widely known as
pathogenic among these bacteria. Then, a phylogenetic tree ofoperational taxonomic units related to Campylobacter was constructed and four species were identified. PCR for these species
identified that the abundance of the genus Campylobacter andCampylobacter ureolyticus was significantly higher in the RAgroup.

Fig. 1: LEfSe analysis
Bacteria common in patients with subarachnoid hemorrhage are shown in red.

Fig. 2: Graphical abstract
The genus Campylobacter and C. ureolyticus may be associated with the ruptureof cerebral aneurysms.

P a t e n t Japanese Patent Application No. 2021-19218
Kawabata, Shuhei; Takagaki, Masatoshi; Kishima, Haruhiko et al. Dysbiosis of Gut Microbiome Is Associated With Rupture of Cerebral Aneurysms.
Tr e a t i s e
Stroke. 2022, Mar; 53(3): 895-903. doi: 10.1161/STROKEAHA.121.034792
URL
K e y w o r d subarachnoid hemorrhage, cerebral aneurysm, gut microbiome