{"doi":"10.1002/alz.70493","title":"The MR1/MAIT cell axis impacts the gut–brain axis through both cognition and microbial community structure in 5XFAD mice","abstract":"INTRODUCTION: Mucosal-associated invariant T (MAIT) cells recognize microbial antigens presented by major histocompatibility complex class I-like molecule (MR1) and are elevated in Alzheimer's disease (AD) model mouse brains; MAIT cell-deficient AD mice have reduced brain pathology, supporting the importance of the gut-brain axis in AD. How the MR1/MAIT cell axis impacts cognition and the microbiome remains unknown. METHODS: Novel object recognition/placement, Y-maze, and Barnes maze were used to determine memory changes in wild-type (WT), MR1 KO, 5XFAD, and 5XFAD/MR1 KO mice. Fecal samples were analyzed using 16S rRNA gene amplicon sequencing. RESULTS: 5XFAD/MR1KO mice did not display the cognitive deficits observed in 5XFAD. There were relative abundance differences in the fecal microbiota between 5XFAD and 5XFAD/MR1 KO mice, and male 5XFAD/MR1 KO mice had increased microbiome alpha diversity compared to 5XFAD mice. DISCUSSION: Our data suggest that the MR1/MAIT cell axis negatively affects cognition and impacts gut microbiome diversity. These results further support a detrimental role for the MR1/MAIT cell axis in AD. HIGHLIGHTS: 5XFAD mice lacking major histocompatibility complex, class I-related (MR1) and mucosal-associated invariant T (MAIT) cells had no deficits in recognition memory. Compared to 5XFAD, there was improved learning in the Barnes maze by female 5XFAD/MR1 knock-out (KO) mice. There was an increased abundance of Campylobacterota in male 5XFAD/MR1 KO versus 5XFAD mice. Six of nine linear discriminant analysis effect size-identified distinguishing features were higher in 5XFAD/MR1 KO mice.","journal":"Alzheimer s & Dementia","year":2025,"id":528533,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9426,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260048,"name":"Jayesh Desai","orcid":"0000-0003-4246-9344","position":1,"is_corresponding":false},{"id":1406864,"name":"Autumn Wireman","orcid":null,"position":2,"is_corresponding":false},{"id":1213964,"name":"Peter Eipers","orcid":null,"position":3,"is_corresponding":false},{"id":418348,"name":"Casey D. Morrow","orcid":"0000-0001-8812-2341","position":4,"is_corresponding":false},{"id":482889,"name":"Jay Vornhagen","orcid":"0000-0002-1685-302X","position":5,"is_corresponding":false},{"id":378955,"name":"Randy R. Brutkiewicz","orcid":"0000-0002-7396-480X","position":6,"is_corresponding":false},{"id":1067990,"name":"Season K. Wyatt‐Johnson","orcid":"0000-0001-8530-7885","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:50:48.492873Z","pmid":"40696831","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":[]}