{"doi":"10.1161/str.50.suppl_1.tmp107","title":"Abstract TMP107: Microbiome Signature of Cerebral Cavernous Malformation Patients","abstract":"<jats:p>\n            <jats:bold>Background:</jats:bold>\n            Cerebral cavernous malformation (CCM) patients have lesions comprised of dilated capillaries in the brain. Despite the knowledge that mutations of three CCM genes can cause this disease, other genetic and environmental factors that contribute to lesion formation are likely given the highly variable disease expression. Genome-wide association studies in CCM cohorts and mouse models of CCM, both point to a role of lipopolysaccharide. Mouse studies have shown that the microbiome, particularly Gram-negative bacteria, drive CCM lesion development. These data point to a possibility that CCM disease is affected by the gut microbiome. In this study, we investigated if human CCM disease could be linked to the gut microbiome.\n          </jats:p>\n          <jats:p>\n            <jats:bold>Methods:</jats:bold>\n            Fecal samples from 88 CCM patients, from four sites, were assayed using 16S rRNA gene sequencing. Following taxonomic classification by exact sequence variant analysis (ESV) using DeBlur, microbiome composition was compared with those of a reference non-CCM population (n=348), or between subgroups of CCM patients based on clinical data elements.\n          </jats:p>\n          <jats:p>\n            <jats:bold>Results:</jats:bold>\n            Analyses of microbiome composition statistics identified bacterial ESVs belonging to Clostridiales\n            <jats:italic>,</jats:italic>\n            Lachnospiraceae, Ruminococcaceae\n            <jats:italic>,</jats:italic>\n            and the genus\n            <jats:italic>Bacteroides</jats:italic>\n            that were significantly enriched in CCM patients compared to healthy controls. Within our CCM cohort, patients with germline\n            <jats:italic>CCM</jats:italic>\n            mutations had stool-associated enrichment of ESVs annotated to Clostridiales, and the genera\n            <jats:italic>Bacteroides</jats:italic>\n            and\n            <jats:italic>Prevotella</jats:italic>\n            , when compared to sporadic CCM patients, while patients with\n            <jats:italic>CCM1</jats:italic>\n            and\n            <jats:italic>CCM2</jats:italic>\n            mutations had different proportions of Clostridiales, Lachnospiraceae, and the genus\n            <jats:italic>Ruminococcus</jats:italic>\n            . Furthermore, Lachnospiraceae and\n            <jats:italic>Bacteroides</jats:italic>\n            proportions differentiated disease aggressiveness (All p&lt;0.05, false discovery rate corrected).\n          </jats:p>\n          <jats:p>\n            <jats:bold>Conclusions:</jats:bold>\n            These data are the first to show that CCM patients have a distinct microbiome signature. Germline mutation and disease aggressiveness can correlate with further unique microbiome composition. This study supports further investigation into the mechanistic link between CCM disease and the microbiome. This will enhance our understanding of the brain-gut axis in CCM disease and the use of microbiome as a therapeutic target.\n          </jats:p>","journal":"Stroke","year":2019,"id":34459,"datarank":0.10843552483759752,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.004463447753605709,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.004463447753605709,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":178444,"name":"Le Shen","orcid":null,"position":1,"is_corresponding":false},{"id":178447,"name":"Anukriti Sharma","orcid":null,"position":2,"is_corresponding":false},{"id":178448,"name":"Agnieszka Stadnik","orcid":null,"position":3,"is_corresponding":false},{"id":178450,"name":"Julian Carrion-Penagos","orcid":null,"position":4,"is_corresponding":false},{"id":178451,"name":"Romuald Girard","orcid":null,"position":5,"is_corresponding":false},{"id":178453,"name":"Janne Koskimäki","orcid":null,"position":6,"is_corresponding":false},{"id":178454,"name":"Sharbel Romanos","orcid":null,"position":7,"is_corresponding":false},{"id":178455,"name":"Seán Lyne","orcid":null,"position":8,"is_corresponding":false},{"id":174178,"name":"Robert Shenkar","orcid":null,"position":9,"is_corresponding":false},{"id":178256,"name":"Ying Cao","orcid":null,"position":10,"is_corresponding":false},{"id":178456,"name":"Kimberly Yan","orcid":null,"position":11,"is_corresponding":false},{"id":178457,"name":"Connie Lee","orcid":null,"position":12,"is_corresponding":false},{"id":178458,"name":"Amy Akers","orcid":null,"position":13,"is_corresponding":false},{"id":178459,"name":"Leslie Morrison","orcid":null,"position":14,"is_corresponding":false},{"id":178460,"name":"Myranda Robinson","orcid":null,"position":15,"is_corresponding":false},{"id":178461,"name":"Atif Zafar","orcid":null,"position":16,"is_corresponding":false},{"id":111725,"name":"Alan Tang","orcid":null,"position":17,"is_corresponding":false},{"id":178462,"name":"Patricia Mericko-Ishizuka","orcid":null,"position":18,"is_corresponding":false},{"id":178463,"name":"Jack A Gilbert","orcid":null,"position":19,"is_corresponding":false},{"id":178464,"name":"Helen Kim","orcid":null,"position":20,"is_corresponding":false},{"id":178465,"name":"Mark Kahn","orcid":null,"position":21,"is_corresponding":false},{"id":178466,"name":"Issam A Awad","orcid":null,"position":22,"is_corresponding":false},{"id":178443,"name":"Sean P Polster","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18998881","pmcid":null,"openalex_id":"https://openalex.org/W2912296760","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.01022753,"influential_citations":0,"citation_trend":[{"year":2025,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://journals.lww.com/00007670-201902001-00516","host_type":"publisher"},{"url":"https://doi.org/10.1161/str.50.suppl_1.tmp107","host_type":"journal"}],"fields_of_study":["Intracerebral and Subarachnoid Hemorrhage Research","Medicine","Biology"],"mesh_terms":[],"keywords":["Lachnospiraceae","Clostridiales","Bacteroidaceae","Ruminococcus","Microbiome","Medicine","Bacteroides","Biology","Genetics","Pathology","Clostridium","16S ribosomal RNA","Gene","Bacteria","Firmicutes"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T18:43:37.712480Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}