{"doi":"10.1101/2021.01.08.425913","title":"Human gut bacteria produce T <sub>H</sub> 17-modulating bile acid metabolites","abstract":"Abstract The microbiota plays a pivotal role in gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17a (T H 17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits T H 17 cell differentiation 1 . While it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown. Furthermore, it was not clear whether 3-oxoLCA and other immunomodulatory bile acids are associated with gut inflammatory pathologies in humans. Using a high-throughput screen, we identified human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite isolithocholic acid (isoLCA). Like 3-oxoLCA, isoLCA suppressed T H 17 differentiation by inhibiting RORγt (retinoic acid receptor-related orphan nuclear receptor γt), a key T H 17 cell-promoting transcription factor. Levels of both 3-oxoLCA and isoLCA and the 3α-hydroxysteroid dehydrogenase (3α-HSDH) genes required for their biosynthesis were significantly reduced in patients with inflammatory bowel diseases (IBD). Moreover, levels of these bile acids were inversely correlated with expression of T H 17 cell-associated genes. Overall, our data suggest that bacterially produced T H 17 cell-inhibitory bile acids may reduce the risk of autoimmune and inflammatory disorders such as IBD.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214291,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":619332,"name":"Lina Yao","orcid":"0000-0003-1018-5646","position":1,"is_corresponding":false},{"id":550202,"name":"Yancong Zhang","orcid":"0000-0002-2768-2975","position":2,"is_corresponding":false},{"id":79202,"name":"Sena Bae","orcid":null,"position":3,"is_corresponding":false},{"id":341143,"name":"Gabriel D. D’Agostino","orcid":null,"position":4,"is_corresponding":false},{"id":628527,"name":"Eunha Kim","orcid":"0000-0001-7041-1727","position":5,"is_corresponding":false},{"id":225246,"name":"Eric A. Franzosa","orcid":"0000-0002-8798-7068","position":6,"is_corresponding":false},{"id":6941,"name":"Julián Ávila-Pacheco","orcid":"0000-0001-9388-3946","position":7,"is_corresponding":false},{"id":301873,"name":"Jordan E. Bisanz","orcid":"0000-0002-8649-1706","position":8,"is_corresponding":false},{"id":808397,"name":"Christopher K. Rakowski","orcid":null,"position":9,"is_corresponding":false},{"id":62275,"name":"Hera Vlamakis","orcid":"0000-0003-1086-9191","position":10,"is_corresponding":false},{"id":104389,"name":"Ramnik J. Xavier","orcid":"0000-0002-5630-5167","position":11,"is_corresponding":false},{"id":36356,"name":"Peter J. Turnbaugh","orcid":"0000-0002-0888-2875","position":12,"is_corresponding":false},{"id":627483,"name":"Randy Longman","orcid":"0000-0002-9042-184X","position":13,"is_corresponding":false},{"id":807737,"name":"Michael R. Krout","orcid":"0000-0002-0539-6986","position":14,"is_corresponding":false},{"id":6946,"name":"Clary B. Clish","orcid":"0000-0001-8259-9245","position":15,"is_corresponding":false},{"id":493,"name":"Curtis Huttenhower","orcid":"0000-0002-1110-0096","position":16,"is_corresponding":false},{"id":619333,"name":"Jun R. Huh","orcid":"0000-0002-1540-6244","position":17,"is_corresponding":false},{"id":44568,"name":"A. Sloan Devlin","orcid":"0000-0001-5598-3751","position":18,"is_corresponding":false},{"id":619330,"name":"Donggi Paik","orcid":"0000-0003-1031-0371","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:52:46.604690Z","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":[]}