| Title: |
Acyloxyacyl hydrolase is a host determinant of gut microbiome-mediated pelvic pain |
| Authors: |
Rahman-Enyart, Afrida; Yang, Wenbin; Yaggie, Ryan E.; White, Bryan A.; Welge, Michael; Auvil, Loretta; Berry, Matthew; Bushell, Colleen; Rosen, John M.; Rudick, Charles N.; Schaeffer, Anthony J.; Klumpp, David J. |
| Contributors: |
Pharmacology and Toxicology, School of Medicine |
| Source: |
PMC |
| Publisher Information: |
The American Physiological Society |
| Publication Year: |
2021 |
| Collection: |
Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| Subject Terms: |
Acyloxyacyl hydrolase; Gut dysbiosis; Interstitial cystitis; Microbiome; Pelvic pain |
| Description: |
Dysbiosis of gut microbiota is associated with many pathologies, yet host factors modulating microbiota remain unclear. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition of chronic pelvic pain often with comorbid urinary dysfunction and anxiety/depression, and recent studies find fecal dysbiosis in patients with IC/BPS. We 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 gastrointestinal (GI) microbiota. AOAH-deficient mice exhibit an enlarged cecum, a phenotype long associated with germ-free rodents, and a "leaky gut" phenotype. AOAH-deficient ceca showed altered gene expression consistent with inflammation, Wnt signaling, and urologic disease. 16S sequencing of stool revealed altered microbiota in AOAH-deficient mice, and GC-MS identified altered metabolomes. Cohousing AOAH-deficient mice with wild-type mice resulted in converged microbiota and altered predicted metagenomes. Cohousing 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 dysbiosis associated with AOAH deficiency contributes to pelvic pain. These findings suggest that the gut microbiome is a potential therapeutic target for IC/BPS. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
American Journal of Physiology: Regulatory, Integrative and Comparative Physiology; https://hdl.handle.net/1805/35297 |
| Availability: |
https://hdl.handle.net/1805/35297 |
| Rights: |
Publisher Policy |
| Accession Number: |
edsbas.B6E89EEF |
| Database: |
BASE |