{"doi":"10.1101/2020.02.29.971242","title":"Dynamics of Gut Microbiome, IgA Response and Plasma Metabolome in Development of Pediatric Celiac Disease","abstract":"SUMMARY Celiac disease (CD) is an autoimmune disorder triggered by gluten consumption. To identify the role of gut microbes in CD onset, we performed a longitudinal study focusing on two important phases of gut microbiota development at ages 2.5 and 5 (n=16). We obtained samples from children who developed CD during or after the study (CD progressors) and age, sex, and HLA-matched healthy controls. CD progressors had a distinct gut microbiota composition and IgA-sequencing identified unique IgA targets in the gut. Three cytokines, one chemokine, and 19 plasma metabolites were significantly altered in CD progressors at age 5. Feeding C57BL/6J mice with taurodeoxycholic acid (TDCA), a 2-fold increased microbiota-derived metabolite in CD progressors, caused villous atrophy, increased intraepithelial lymphocytes (IELs), CD4+ T-cells, Natural Killer cells, and Qa-1 expression on T-cells while decreasing T-regulatory cells in IELs. Thus, TDCA drives inflammation in the small intestines that potentially contribute to the CD onset. Highlights CD progressors have a distinct gut microbiome composition compared to healthy controls in two important phases of gut microbiota development (age 2.5 and 5 years) CD progressors have more IgA-coated bacteria in their gut at age 5 compared to healthy controls. Further, IgA-sequencing identified unique bacterial targets in CD progressors. Three plasma proinflammatory cytokines and a chemokine were increased in CD progressors years before diagnosis, indicating an early inflammatory response. We identified 19 metabolites that are significantly altered in CD progress at age 5 and microbiota-derived TDCA increased two-fold. TDCA treatment in B6 mice increased CD4+ cells and NK cells while decreasing CD8+ T-regulatory (Treg) cells. It also increased Qa-1 expression on immune cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120653,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9106,"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":254150,"name":"Qian Huang","orcid":"0000-0002-2209-3661","position":1,"is_corresponding":false},{"id":559742,"name":"Yusuf Dogus Dogru","orcid":null,"position":2,"is_corresponding":false},{"id":558668,"name":"Yi Yang","orcid":"0000-0002-5200-0614","position":3,"is_corresponding":false},{"id":258924,"name":"Vladimir Tolstikov","orcid":"0000-0002-0445-884X","position":4,"is_corresponding":false},{"id":558669,"name":"Martina Chrudinová","orcid":"0000-0003-2998-9476","position":5,"is_corresponding":false},{"id":559743,"name":"Amol Raisingani","orcid":null,"position":6,"is_corresponding":false},{"id":109513,"name":"Jonas F. Ludvigsson","orcid":"0000-0003-1024-5602","position":7,"is_corresponding":false},{"id":258929,"name":"Michael A. Kiebish","orcid":"0000-0002-5678-0072","position":8,"is_corresponding":false},{"id":36386,"name":"Noah W. Palm","orcid":"0000-0001-7262-9455","position":9,"is_corresponding":false},{"id":254151,"name":"Johnny Ludvigsson","orcid":"0000-0003-1695-5234","position":10,"is_corresponding":false},{"id":254152,"name":"Emrah Altındiş","orcid":"0000-0001-9657-7602","position":11,"is_corresponding":false},{"id":558667,"name":"Khyati Girdhar","orcid":"0000-0002-6823-6410","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-18T23:14:38.147936Z","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":[]}