{"doi":"10.1016/j.celrep.2024.114891","title":"A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity","abstract":"Diet can protect from autoimmune disease; however, whether diet acts via the host and/or microbiome remains unclear. Here, we use a ketogenic diet (KD) as a model to dissect these complex interactions. A KD rescued the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis in a microbiota-dependent fashion. Dietary supplementation with a single KD-dependent host metabolite (β-hydroxybutyrate [βHB]) rescued EAE, whereas transgenic mice unable to produce βHB in the intestine developed more severe disease. Transplantation of the βHB-shaped gut microbiota was protective. Lactobacillus sequence variants were associated with decreased T helper 17 cell activation in vitro. Finally, we isolated an L. murinus strain that protected from EAE, which was phenocopied by a Lactobacillus metabolite enriched by βHB supplementation, indole lactate. Thus, diet alters the immunomodulatory potential of the gut microbiota by shifting host metabolism, emphasizing the utility of taking a more integrative approach to study diet-host-microbiome interactions.","journal":"Cell Reports","year":2024,"id":421722,"datarank":0.9260030232789485,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.41582341602962497,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.41582341602962497,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":26,"citers_with_citation_signal":16,"citers_with_endowment":16,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"is_data_producer":true,"deposit_databanks":{"BioProject":["PRJNA1032118"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":36357,"name":"Vaibhav Upadhyay","orcid":"0000-0002-7652-1043","position":1,"is_corresponding":false},{"id":1163895,"name":"Rachel Rock","orcid":null,"position":2,"is_corresponding":false},{"id":869261,"name":"Lorenzo Ramirez","orcid":null,"position":3,"is_corresponding":false},{"id":827097,"name":"Kai Trepka","orcid":"0000-0002-8672-6317","position":4,"is_corresponding":false},{"id":261889,"name":"Patrycja Puchalska","orcid":"0000-0002-1875-1203","position":5,"is_corresponding":false},{"id":1163423,"name":"Diego Orellana","orcid":"0000-0002-1337-8630","position":6,"is_corresponding":false},{"id":260536,"name":"Qi Yan Ang","orcid":"0000-0002-9788-1283","position":7,"is_corresponding":false},{"id":235388,"name":"Caroline Whitty","orcid":"0000-0002-8744-037X","position":8,"is_corresponding":false},{"id":623133,"name":"Jessie A. Turnbaugh","orcid":"0000-0003-3933-1985","position":9,"is_corresponding":false},{"id":239560,"name":"Yuan Tian","orcid":"0000-0001-6174-3359","position":10,"is_corresponding":false},{"id":1163424,"name":"Darren S. Dumlao","orcid":"0009-0000-0182-072X","position":11,"is_corresponding":false},{"id":554712,"name":"Renuka R. Nayak","orcid":"0000-0002-1123-4668","position":12,"is_corresponding":false},{"id":239569,"name":"Andrew D. Patterson","orcid":"0000-0003-2073-0070","position":13,"is_corresponding":false},{"id":228957,"name":"John C. Newman","orcid":"0000-0002-8455-0100","position":14,"is_corresponding":false},{"id":261898,"name":"Peter A. Crawford","orcid":"0000-0001-8597-4426","position":15,"is_corresponding":false},{"id":36356,"name":"Peter J. Turnbaugh","orcid":"0000-0002-0888-2875","position":16,"is_corresponding":false},{"id":256564,"name":"Margaret Alexander","orcid":"0000-0003-2972-7521","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-19T01:57:41.370244Z","pmid":"39500329","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":[]}