Browsing by Author "Rudick, Charles N."

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    Acyloxyacyl hydrolase is a host determinant of gut microbiome-mediated pelvic pain
    (The American Physiological Society, 2021) 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.; Pharmacology and Toxicology, School of Medicine
    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.
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    Author Correction: Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction
    (SpringerNature, 2018-04-16) Rodriguez-Nunez, Ivan; Caluag, Tiffany; Kirby, Kori; Rudick, Charles N.; Dziarski, Roman; Gupta, Dipika; Medicine, School of Medicine
    A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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    Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction
    (SpringerNature, 2017-04-03) Rodriguez-Nunez, Ivan; Caluag, Tiffany; Kirby, Kori; Rudick, Charles N.; Dziarski, Roman; Gupta, Dipika; Department of Medicine, School of Medicine
    Genetics plays a central role in susceptibility to obesity and metabolic diseases. BALB/c mice are known to be resistant to high fat diet (HFD)-induced obesity, however the genetic cause remains unknown. We report that deletion of the innate immunity antibacterial gene Nod2 abolishes this resistance, as Nod2 -/- BALB/c mice developed HFD-dependent obesity and hallmark features of metabolic syndrome. Nod2 -/- HFD mice developed hyperlipidemia, hyperglycemia, glucose intolerance, increased adiposity, and steatosis, with large lipid droplets in their hepatocytes. These changes were accompanied by increased expression of immune genes in adipose tissue and differential expression of genes for lipid metabolism, signaling, stress, transport, cell cycle, and development in both adipose tissue and liver. Nod2 -/- HFD mice exhibited changes in the composition of the gut microbiota and long-term treatment with antibiotics abolished diet-dependent weight gain in Nod2 -/- mice, but not in wild type mice. Furthermore, microbiota from Nod2 -/- HFD mice transferred sensitivity to weight gain, steatosis, and hyperglycemia to wild type germ free mice. In summary, we have identified a novel role for Nod2 in obesity and demonstrate that Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction.