{"doi":"10.1101/2021.01.27.428290","title":"Acyloxyacyl Hydrolase is a Host Determinant of Gut Microbiome-Mediated Pelvic Pain","abstract":"ABSTRACT Dysbiosis of gut microbiota is associated with many pathologies, yet host factors modulating microbiota remain unclear. Interstitial cystitis/bladder pain syndrome (IC/BPS or “IC”) is a debilitating condition of chronic pelvic pain often with co-morbid urinary dysfunction and anxiety/depression, and recent studies find fecal dysbiosis in IC/BPS patients. We previously identified the locus encoding acyloxyacyl hydrolase, Aoah , as a modulator of pelvic pain severity in a murine IC/BPS model. AOAH-deficient mice spontaneously develop rodent correlates of pelvic pain, increased responses to induced pelvic pain models, voiding dysfunction, and anxious/depressive behaviors. Here, we report that AOAH-deficient mice exhibit dysbiosis of GI microbiota. AOAH-deficient mice exhibit an enlarged cecum, a phenotype long associated with germ-free rodents, and reduced trans-epithelial electrical resistance consistent with a “leaky gut” phenotype. AOAH-deficient ceca showed altered gene expression consistent with inflammation, Wnt signaling, and urologic disease. 16S rRNA sequencing of stool revealed altered microbiota in AOAH-deficient mice, and GC-MS identified altered metabolomes. Co-housing AOAH-deficient mice with wild type mice resulted in converged microbiota and altered predicted metagenomes. Co-housing also abrogated the pelvic pain phenotype of AOAH-deficient mice, which was corroborated by oral gavage of AOAH-deficient mice with stool slurry of wild type mice. Converged microbiota also alleviated comorbid anxiety-like behavior in AOAH-deficient mice. Oral gavage of AOAH-deficient mice with anaerobes cultured from IC/BPS stool resulted in exacerbation of pelvic allodynia. Together, these data indicate that AOAH is a host determinant of normal gut microbiota, and the dysbiosis associated with AOAH deficiency contributes to pelvic pain. These findings suggest that the gut microbiome is a potential therapeutic target for IC/BPS.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216337,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":384950,"name":"Wen‐Bin Yang","orcid":"0000-0002-6497-4176","position":1,"is_corresponding":false},{"id":455895,"name":"Ryan E. Yaggie","orcid":null,"position":2,"is_corresponding":false},{"id":252211,"name":"Bryan A. White","orcid":"0000-0002-9107-1167","position":3,"is_corresponding":false},{"id":441065,"name":"Michael Welge","orcid":null,"position":4,"is_corresponding":false},{"id":173896,"name":"Loretta Auvil","orcid":null,"position":5,"is_corresponding":false},{"id":812243,"name":"Matthew Berry","orcid":"0000-0003-0068-4812","position":6,"is_corresponding":false},{"id":329658,"name":"Colleen Bushell","orcid":"0000-0002-5268-1915","position":7,"is_corresponding":false},{"id":812244,"name":"John M. Rosen","orcid":"0000-0003-4291-3214","position":8,"is_corresponding":false},{"id":812759,"name":"Charles N. Rudick","orcid":null,"position":9,"is_corresponding":false},{"id":455204,"name":"Anthony J. Schaeffer","orcid":"0000-0002-1324-3517","position":10,"is_corresponding":false},{"id":455205,"name":"David J. Klumpp","orcid":"0000-0002-1237-8364","position":11,"is_corresponding":false},{"id":812758,"name":"Afrida Rahman-Enyart","orcid":null,"position":0,"is_corresponding":true}],"reference_count":136,"raw_metadata":null,"created_at":"2026-07-18T23:53:11.245932Z","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":[]}