{"doi":"10.7554/elife.104121","title":"Complex system modeling reveals oxalate homeostasis is driven by diverse oxalate-degrading bacteria","abstract":"Decades of research have made clear that host-associated microbiomes touch all facets of health. However, effective therapies that target the microbiome have been elusive given its inherent complexity. Here, we experimentally examined diet-microbe-host interactions through a complex systems framework, centered on dietary oxalate. Using multiple, independent molecular, rodent, and in vitro experimental models, we found that microbiome composition influenced multiple oxalate-microbe-host interfaces. Importantly, the administration of the oxalate-degrading specialist, Oxalobacter formigenes, was only effective against a poor oxalate-degrading microbiota background and gives critical new insights into why clinical intervention trials with this species exhibit variable outcomes. Data suggest that, while heterogeneity in the microbiome impacts multiple diet-host-microbe interfaces, metabolic redundancy among diverse microorganisms in specific diet-microbe axes is a critical variable that may impact the efficacy of bacteriotherapies, which can help guide patient and probiotic selection criteria in probiotic clinical trials.","journal":"eLife","year":2025,"id":555400,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9481,"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":1453693,"name":"Carlos Batagello","orcid":"0000-0002-7240-7956","position":1,"is_corresponding":false},{"id":1454187,"name":"Ava Adler","orcid":null,"position":2,"is_corresponding":false},{"id":1454188,"name":"Jose Agudelo","orcid":null,"position":3,"is_corresponding":false},{"id":1454189,"name":"Anna Zampini","orcid":null,"position":4,"is_corresponding":false},{"id":1380763,"name":"Mangesh Suryavanshi","orcid":"0000-0002-6054-3926","position":5,"is_corresponding":false},{"id":893958,"name":"Andrew Nguyen","orcid":"0000-0001-5362-4456","position":6,"is_corresponding":false},{"id":632983,"name":"Teri J. Orr","orcid":"0000-0001-6247-5237","position":7,"is_corresponding":false},{"id":632985,"name":"M. Denise Dearing","orcid":"0000-0001-7881-4934","position":8,"is_corresponding":false},{"id":1453694,"name":"Manoj Monga","orcid":"0000-0001-6419-413X","position":9,"is_corresponding":false},{"id":393118,"name":"Aaron W. Miller","orcid":"0000-0001-8342-1449","position":10,"is_corresponding":false},{"id":524150,"name":"Sromona Mukherjee","orcid":"0000-0003-1958-0220","position":0,"is_corresponding":true}],"reference_count":156,"raw_metadata":null,"created_at":"2026-07-19T02:54:59.329539Z","pmid":"40310467","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":[]}