{"doi":"10.3390/metabo12070645","title":"Microbial Metabolite 3-Indolepropionic Acid Mediates Immunosuppression","abstract":"The microbial-derived metabolite, 3-indolepropionic acid (3-IPA), has been intensely studied since its origins were discovered in 2009; however, 3-IPA’s role in immunosuppression has had limited attention. Untargeted metabolomic analyses of T-cell exhaustion and immunosuppression, represented by dysfunctional under-responsive CD8+ T cells, reveal a potential role of 3-IPA in these responses. T-cell exhaustion was examined via infection of two genetically related mouse strains, DBA/1J and DBA/2J, with lymphocytic choriomeningitis virus (LCMV) Clone 13 (Cl13). The different mouse strains produced disparate outcomes driven by their T-cell responses. Infected DBA/2J presented with exhausted T cells and persistent infection, and DBA/1J mice died one week after infection from cytotoxic T lymphocytes (CTLs)-mediated pulmonary failure. Metabolomics revealed over 70 metabolites were altered between the DBA/1J and DBA/2J models over the course of the infection, most of them in mice with a fatal outcome. Cognitive-driven prioritization combined with statistical significance and fold change were used to prioritize the metabolites. 3-IPA, a tryptophan-derived metabolite, was identified as a high-priority candidate for testing. To test its activity 3-IPA was added to the drinking water of the mouse models during LCMV Cl13 infection, with the results showing that 3-IPA allowed the mice to survive longer. This negative immune-modulation effect might be of interest for the modulation of CTL responses in events such as autoimmune diseases, type I diabetes or even COVID-19. Moreover, 3-IPA’s bacterial origin raises the possibility of targeting the microbiome to enhance CTL responses in diseases such as cancer and chronic infection.","journal":"Metabolites","year":2022,"id":254541,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":626684,"name":"Lucy E. Horton","orcid":null,"position":1,"is_corresponding":false},{"id":901656,"name":"Linh Hoang","orcid":"0000-0002-0077-8213","position":2,"is_corresponding":false},{"id":857934,"name":"Xavier Domingo-Almenara","orcid":"0000-0002-0133-6863","position":3,"is_corresponding":false},{"id":706816,"name":"Elizabeth Billings","orcid":"0000-0002-4320-3276","position":4,"is_corresponding":false},{"id":499382,"name":"Brian C. Ware","orcid":"0000-0001-7806-3456","position":5,"is_corresponding":false},{"id":251093,"name":"Brian M. Sullivan","orcid":"0000-0003-4277-6037","position":6,"is_corresponding":false},{"id":113550,"name":"Gary Siuzdak","orcid":"0000-0002-4749-0014","position":7,"is_corresponding":false},{"id":273644,"name":"Carlos Guijas","orcid":"0000-0001-7993-3388","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:08.518416Z","pmid":"35888769","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":[]}