{"doi":"10.1016/j.jcmgh.2020.08.002","title":"Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain Axis","abstract":"BACKGROUND & AIMS: The human gut microbiota can regulate production of serotonin (5-hydroxytryptamine [5-HT]) from enterochromaffin cells. However, the mechanisms underlying microbial-induced serotonin signaling are not well understood. METHODS: Adult germ-free mice were treated with sterile media, live Bifidobacterium dentium, heat-killed B dentium, or live Bacteroides ovatus. Mouse and human enteroids were used to assess the effects of B dentium metabolites on 5-HT release from enterochromaffin cells. In vitro and in vivo short-chain fatty acids and 5-HT levels were assessed by mass spectrometry. Expression of tryptophan hydroxylase, short-chain fatty acid receptor free fatty acid receptor 2, 5-HT receptors, and the 5-HT re-uptake transporter (serotonin transporter) were assessed by quantitative polymerase chain reaction and immunostaining. RNA in situ hybridization assessed 5-HT-receptor expression in the brain, and 5-HT-receptor-dependent behavior was evaluated using the marble burying test. RESULTS: B dentium mono-associated mice showed increased fecal acetate. This finding corresponded with increased intestinal 5-HT concentrations and increased expression of 5-HT receptors 2a, 4, and serotonin transporter. These effects were absent in B ovatus-treated mice. Application of acetate and B dentium-secreted products stimulated 5-HT release in mouse and human enteroids. In situ hybridization of brain tissue also showed significantly increased hippocampal expression of 5-HT-receptor 2a in B dentium-treated mice relative to germ-free controls. Functionally, B dentium colonization normalized species-typical repetitive and anxiety-like behaviors previously shown to be linked to 5-HT-receptor 2a. CONCLUSIONS: These data suggest that B dentium, and the bacterial metabolite acetate, are capable of regulating key components of the serotonergic system in multiple host tissues, and are associated with a functional change in adult behavior.","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2020,"id":51352,"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":159,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255979,"name":"Berkley Luck","orcid":"0000-0001-5996-876X","position":1,"is_corresponding":false},{"id":255980,"name":"Chonnikant Visuthranukul","orcid":"0000-0003-1693-2550","position":2,"is_corresponding":false},{"id":255981,"name":"Faith D. Ihekweazu","orcid":"0000-0002-9800-8590","position":3,"is_corresponding":false},{"id":255982,"name":"Amy C. Engevik","orcid":"0000-0001-9108-3240","position":4,"is_corresponding":false},{"id":255983,"name":"Zhongcheng Shi","orcid":"0000-0001-9267-4536","position":5,"is_corresponding":false},{"id":255984,"name":"Heather A. Danhof","orcid":"0000-0002-6347-0021","position":6,"is_corresponding":false},{"id":255985,"name":"Alexandra L. Chang‐Graham","orcid":"0000-0002-3403-6787","position":7,"is_corresponding":false},{"id":255986,"name":"Anne Hall","orcid":"0000-0001-6814-6514","position":8,"is_corresponding":false},{"id":257270,"name":"Bradley T. Endres","orcid":null,"position":9,"is_corresponding":false},{"id":255987,"name":"Sigmund J. Haidacher","orcid":"0000-0002-6103-1906","position":10,"is_corresponding":false},{"id":255988,"name":"Thomas D. Horvath","orcid":"0000-0001-9761-3484","position":11,"is_corresponding":false},{"id":255989,"name":"Anthony M. Haag","orcid":"0000-0002-3547-2812","position":12,"is_corresponding":false},{"id":255990,"name":"Sridevi Devaraj","orcid":"0000-0001-9189-7914","position":13,"is_corresponding":false},{"id":255991,"name":"Kevin W. Garey","orcid":"0000-0003-2063-7503","position":14,"is_corresponding":false},{"id":255992,"name":"Robert A. Britton","orcid":"0000-0001-8983-9539","position":15,"is_corresponding":false},{"id":255993,"name":"Joseph M. Hyser","orcid":"0000-0001-5249-3482","position":16,"is_corresponding":false},{"id":255994,"name":"Noah F. Shroyer","orcid":"0000-0002-5934-2852","position":17,"is_corresponding":false},{"id":29028,"name":"James Versalovic","orcid":"0000-0002-5765-4385","position":18,"is_corresponding":false},{"id":255978,"name":"Melinda A. Engevik","orcid":"0000-0002-9742-9932","position":0,"is_corresponding":true}],"reference_count":161,"raw_metadata":null,"created_at":"2026-07-18T20:40:28.278215Z","pmid":"32795610","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":[]}