{"doi":"10.64898/2026.04.27.721133","title":"Gut microbiota-derived indole-3-propionic acid preserves dorsal hippocampal catecholamines to prevent post-stroke cognitive impairment","abstract":"<jats:title>Abstract</jats:title>\n                <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>Gut dysbiosis has been increasingly implicated in post-stroke cognitive impairment (PSCI), yet the causal contribution and therapeutic potential of gut microbiota-derived metabolites remain unclear. This study aimed to identify key microbiota-derived metabolites involved in PSCI and to elucidate their underlying mechanisms.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>We found that both PSCI patients and middle cerebral artery occlusion (MCAO) mice exhibited distinct gut microbial alterations, characterized by a marked reduction in tryptophan-metabolizing bacteria and indole-3-propionic acid (IPA), a gut microbiota-derived tryptophan metabolite. Exogenous IPA administration alleviated PSCI-like phenotypes in MCAO mice. Mechanistically, IPA preserved tyrosine hydroxylase-positive (Th⁺) fibers and catecholamine levels in the dorsal hippocampus. Further analyses showed that IPA binds to the adaptor protein Ywhab, promotes ERK activation, and enhances neuronal survival, thereby counteracting neuronal apoptosis-associated inflammation and subsequent Th⁺ fiber degeneration.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>These findings identify IPA as a gut microbiota-derived neuromodulator that mitigates PSCI by preserving dorsal hippocampal catecholaminergic transmission. IPA may therefore serve as a promising predictive biomarker and therapeutic candidate for PSCI.</jats:p>\n                </jats:sec>","journal":null,"year":null,"id":663136,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":1615865,"name":"Huaying Zhang","orcid":"0000-0003-2727-9884","position":1,"is_corresponding":false},{"id":1731249,"name":"Fangbo Xia","orcid":null,"position":2,"is_corresponding":false},{"id":1731250,"name":"Xuxuan Gao","orcid":"0009-0007-5558-7012","position":3,"is_corresponding":false},{"id":1147774,"name":"Zhuang Li","orcid":"0009-0008-6586-3989","position":4,"is_corresponding":false},{"id":305657,"name":"Xin Zhao","orcid":"0000-0001-8502-0139","position":5,"is_corresponding":false},{"id":1401911,"name":"Fan Wu","orcid":"0000-0003-1845-437X","position":6,"is_corresponding":false},{"id":1731251,"name":"Mengxi Li","orcid":null,"position":7,"is_corresponding":false},{"id":1370852,"name":"Kaiyu Xu","orcid":"0000-0001-9685-9060","position":8,"is_corresponding":false},{"id":1731252,"name":"Muxuan Chen","orcid":"0000-0002-8961-2649","position":9,"is_corresponding":false},{"id":1731253,"name":"Ranyue Ren","orcid":null,"position":10,"is_corresponding":false},{"id":1731254,"name":"Weike Hu","orcid":null,"position":11,"is_corresponding":false},{"id":295211,"name":"Jia Yin","orcid":"0000-0003-1340-6758","position":12,"is_corresponding":false},{"id":255423,"name":"Hongwei Zhou","orcid":"0000-0003-2472-8541","position":13,"is_corresponding":false},{"id":1731255,"name":"Dongxin Zhang","orcid":null,"position":14,"is_corresponding":false},{"id":555362,"name":"Yisi Liu","orcid":"0000-0001-6974-1462","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Gut microbiota-derived indole-3-propionic acid preserves dorsal hippocampal catecholamines to prevent post-stroke cognitive impairment","abstract":"<jats:title>Abstract</jats:title>\n                <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>Gut dysbiosis has been increasingly implicated in post-stroke cognitive impairment (PSCI), yet the causal contribution and therapeutic potential of gut microbiota-derived metabolites remain unclear. This study aimed to identify key microbiota-derived metabolites involved in PSCI and to elucidate their underlying mechanisms.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>We found that both PSCI patients and middle cerebral artery occlusion (MCAO) mice exhibited distinct gut microbial alterations, characterized by a marked reduction in tryptophan-metabolizing bacteria and indole-3-propionic acid (IPA), a gut microbiota-derived tryptophan metabolite. Exogenous IPA administration alleviated PSCI-like phenotypes in MCAO mice. Mechanistically, IPA preserved tyrosine hydroxylase-positive (Th⁺) fibers and catecholamine levels in the dorsal hippocampus. Further analyses showed that IPA binds to the adaptor protein Ywhab, promotes ERK activation, and enhances neuronal survival, thereby counteracting neuronal apoptosis-associated inflammation and subsequent Th⁺ fiber degeneration.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>These findings identify IPA as a gut microbiota-derived neuromodulator that mitigates PSCI by preserving dorsal hippocampal catecholaminergic transmission. IPA may therefore serve as a promising predictive biomarker and therapeutic candidate for PSCI.</jats:p>\n                </jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19162232","pmcid":null,"openalex_id":"https://openalex.org/W7160204330","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://creativecommons.org/licenses/by-nc-nd/4.0/","oa_locations":[{"url":"https://syndication.highwire.org/content/doi/10.64898/2026.04.27.721133","host_type":"publisher"},{"url":"https://doi.org/10.64898/2026.04.27.721133","host_type":"repository"}],"fields_of_study":["Gut microbiota and health","Neuroinflammation and Neurodegeneration Mechanisms","Tryptophan and brain disorders"],"mesh_terms":[],"keywords":["Hippocampal formation","Catecholaminergic","Biomarker","Catecholamine","Dorsum","Serotonin","Central nervous system","Dopamine","Nociception"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T19:53:37.492436Z","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":[]}